Beclin 1-Vps34 complex architecture: Understanding the nuts and bolts of therapeutic targets
Deanna H. Morris, Calvin K. Yip, Yi Shi, Brian T. Chait, Qing Jun Wang
Beclin 1-Vps34 complex architecture: Understanding the nuts and bolts of therapeutic targets
Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin 1-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.
Beclin 1 / Vps34 / Nrbf2 / complex / structure / CX-MS / EM / inhibitor / drug design
[1] |
Aita V M, Liang X H, Murty V V, Pincus D L, Yu W, Cayanis E, Kalachikov S, Gilliam T C, Levine B (1999). Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics, 59(1): 59–65
CrossRef
Pubmed
Google scholar
|
[2] |
Araki Y, Ku W C, Akioka M, May A I, Hayashi Y, Arisaka F, Ishihama Y, Ohsumi Y (2013). Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity. J Cell Biol, 203(2): 299–313
CrossRef
Pubmed
Google scholar
|
[3] |
Arena G, Gelmetti V, Torosantucci L, Vignone D, Lamorte G, De Rosa P, Cilia E, Jonas E A, Valente E M (2013). PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage. Cell Death Differ, 20(7): 920–930
CrossRef
Pubmed
Google scholar
|
[4] |
Arroyo D S, Gaviglio E A, Peralta Ramos J M, Bussi C, Rodriguez-Galan M C, Iribarren P (2014). Autophagy in inflammation, infection, neurodegeneration and cancer. Int Immunopharmacol, 18(1): 55–65
CrossRef
Pubmed
Google scholar
|
[5] |
Arsov I, Adebayo A, Kucerova-Levisohn M, Haye J, MacNeil M, Papavasiliou F N, Yue Z, Ortiz B D (2011). A role for autophagic protein beclin 1 early in lymphocyte development. J Immunol, 186(4): 2201–2209
CrossRef
Pubmed
Google scholar
|
[6] |
Arsov I, Li X, Matthews G, Coradin J, Hartmann B, Simon A K, Sealfon S C, Yue Z (2008). BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development. Cell Death Differ, 15(9): 1385–1395
CrossRef
Pubmed
Google scholar
|
[7] |
Axe E L, Walker S A, Manifava M, Chandra P, Roderick H L, Habermann A, Griffiths G, Ktistakis N T (2008). Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol, 182(4): 685–701
CrossRef
Pubmed
Google scholar
|
[8] |
Backer J M (2008). The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem J, 410(1): 1–17
CrossRef
Pubmed
Google scholar
|
[9] |
Bago R, Malik N, Munson M J, Prescott A R, Davies P, Sommer E, Shpiro N, Ward R, Cross D, Ganley I G, Alessi D R (2014). Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. Biochem J, 463(3): 413–427
CrossRef
Pubmed
Google scholar
|
[10] |
Bai L, Wang S (2014). Targeting apoptosis pathways for new cancer therapeutics. Annu Rev Med, 65(1): 139–155
CrossRef
Pubmed
Google scholar
|
[11] |
Baskaran S, Carlson L A, Stjepanovic G, Young L N, Kim D J, Grob P, Stanley R E, Nogales E, Hurley J H (2015). Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex. eLife, 3: e05115
|
[12] |
Behrends C, Sowa M E, Gygi S P, Harper J W (2010). Network organization of the human autophagy system. Nature, 466(7302): 68–76
CrossRef
Pubmed
Google scholar
|
[13] |
Bergamini E, Cavallini G, Donati A, Gori Z (2007). The role of autophagy in aging: its essential part in the anti-aging mechanism of caloric restriction. Ann N Y Acad Sci, 1114(1): 69–78
CrossRef
Pubmed
Google scholar
|
[14] |
Blommaart E F, Krause U, Schellens J P, Vreeling-Sindelárová H, Meijer A J (1997). The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem, 243(1–2): 240–246
CrossRef
Pubmed
Google scholar
|
[15] |
Bodemann B O, Orvedahl A, Cheng T, Ram R R, Ou Y H, Formstecher E, Maiti M, Hazelett C C, Wauson E M, Balakireva M, Camonis J H, Yeaman C, Levine B, White M A (2011). RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. Cell, 144(2): 253–267
CrossRef
Pubmed
Google scholar
|
[16] |
Brunk U T, Terman A (2002). The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem, 269(8): 1996–2002
CrossRef
Pubmed
Google scholar
|
[17] |
Budovskaya Y V, Hama H, DeWald D B, Herman P K (2002). The C terminus of the Vps34p phosphoinositide 3-kinase is necessary and sufficient for the interaction with the Vps15p protein kinase. J Biol Chem, 277(1): 287–294
CrossRef
Pubmed
Google scholar
|
[18] |
Burgess M R, Skaggs B J, Shah N P, Lee F Y, Sawyers C L (2005). Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA, 102(9): 3395–3400
CrossRef
Pubmed
Google scholar
|
[19] |
Byfield M P, Murray J T, Backer J M (2005). hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem, 280(38): 33076–33082
CrossRef
Pubmed
Google scholar
|
[20] |
Cao C, Backer J M, Laporte J, Bedrick E J, Wandinger-Ness A (2008). Sequential actions of myotubularin lipid phosphatases regulate endosomal PI(3)P and growth factor receptor trafficking. Mol Biol Cell, 19(8): 3334–3346
CrossRef
Pubmed
Google scholar
|
[21] |
Cao C, Laporte J, Backer J M, Wandinger-Ness A, Stein M P (2007). Myotubularin lipid phosphatase binds the hVPS15/hVPS34 lipid kinase complex on endosomes. Traffic, 8(8): 1052–1067
CrossRef
Pubmed
Google scholar
|
[22] |
Cao Y, Wang Y, Abi Saab W F, Yang F, Pessin J E, Backer J M (2014). NRBF2 regulates macroautophagy as a component of Vps34 Complex I. Biochem J, 461(2): 315–322
CrossRef
Pubmed
Google scholar
|
[23] |
Chew L H, Yip C K (2014). Structural biology of the macroautophagy machinery. Frontiers in Biology, 9(1): 18–34
CrossRef
Google scholar
|
[24] |
Choi A M, Ryter S W, Levine B (2013). Autophagy in human health and disease. N Engl J Med, 368(7): 651–662
CrossRef
Pubmed
Google scholar
|
[25] |
Choubey V, Cagalinec M, Liiv J, Safiulina D, Hickey M A, Kuum M, Liiv M, Anwar T, Eskelinen E L, Kaasik A (2014). BECN1 is involved in the initiation of mitophagy: it facilitates PARK2 translocation to mitochondria. Autophagy, 10(6): 1105–1119
CrossRef
Pubmed
Google scholar
|
[26] |
Christoforidis S, Miaczynska M, Ashman K, Wilm M, Zhao L, Yip S C, Waterfield M D, Backer J M, Zerial M (1999). Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat Cell Biol, 1(4): 249–252
CrossRef
Pubmed
Google scholar
|
[27] |
Ciccarelli F D, Proukakis C, Patel H, Cross H, Azam S, Patton M A, Bork P, Crosby A H (2003). The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. Genomics, 81(4): 437–441
CrossRef
Pubmed
Google scholar
|
[28] |
Cuervo A M (2008). Calorie restriction and aging: the ultimate “cleansing diet”. J Gerontol A Biol Sci Med Sci, 63(6): 547–549
CrossRef
Pubmed
Google scholar
|
[29] |
Darabi H, McCue K, Beesley J, Michailidou K, Nord S, Kar S, Humphreys K, Thompson D, Ghoussaini M, Bolla M K, Dennis J, Wang Q, Canisius S, Scott C G, Apicella C, Hopper J L, Southey M C, Stone J, Broeks A, Schmidt M K, Scott R J, Lophatananon A, Muir K, Beckmann M W, Ekici A B, Fasching P A, Heusinger K, Dos-Santos-Silva I, Peto J, Tomlinson I, Sawyer E J, Burwinkel B, Marme F, Guánel P, Truong T, Bojesen S E, Flyger H, Benitez J, González-Neira A, Anton-Culver H, Neuhausen S L, Arndt V, Brenner H, Engel C, Meindl A, Schmutzler R K, Arnold N, Brauch H, Hamann U, Chang-Claude J, Khan S, Nevanlinna H, Ito H, Matsuo K, Bogdanova N V, Dárk T, Lindblom A, Margolin S, Kosma V M, Mannermaa A, Tseng C C, Wu A H, Floris G, Lambrechts D, Rudolph A, Peterlongo P, Radice P, Couch F J, Vachon C, Giles G G, McLean C, Milne R L, Dugué P A, Haiman C A, Maskarinec G, Woolcott C, Henderson B E, Goldberg M S, Simard J, Teo S H, Mariapun S, Helland Å, Haakensen V, Zheng W, Beeghly-Fadiel A, Tamimi R, Jukkola-Vuorinen A, Winqvist R, Andrulis I L, Knight J A, Devilee P, Tollenaar R A, Figueroa J, García-Closas M, Czene K, Hooning M J, Tilanus-Linthorst M, Li J, Gao Y T, Shu X O, Cox A, Cross S S, Luben R, Khaw K T, Choi J Y, Kang D, Hartman M, Lim W Y, Kabisch M, Torres D, Jakubowska A, Lubinski J, McKay J, Sangrajrang S, Toland A E, Yannoukakos D, Shen C Y, Yu J C, Ziogas A, Schoemaker M J, Swerdlow A, Borresen-Dale A L, Kristensen V, French J D, Edwards S L, Dunning A M, Easton D F, Hall P, Chenevix-Trench G, and the German Consortium of Hereditary Breast and Ovarian Cancer, and the kConFab/AOCS Investigators (2015). Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression. Am J Hum Genet, 97(1): 22–34
CrossRef
Pubmed
Google scholar
|
[30] |
Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y, Zhou Q, Wilz L M, Li J, Vivona S, Pfuetzner R A, Brunger A T, Zhong Q (2015). ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature, 520(7548): 563–566
CrossRef
Pubmed
Google scholar
|
[31] |
Dooley H C, Razi M, Polson H E, Girardin S E, Wilson M I, Tooze S A (2014). WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. Mol Cell, 55(2): 238–252
CrossRef
Pubmed
Google scholar
|
[32] |
Dou Z, Chattopadhyay M, Pan J A, Guerriero J L, Jiang Y P, Ballou L M, Yue Z, Lin R Z, Zong W X (2010). The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy. J Cell Biol, 191(4): 827–843
CrossRef
Pubmed
Google scholar
|
[33] |
Dou Z, Pan J A, Dbouk H A, Ballou L M, DeLeon J L, Fan Y, Chen J S, Liang Z, Li G, Backer J M, Lin R Z, Zong W X (2013). Class IA PI3K p110β subunit promotes autophagy through Rab5 small GTPase in response to growth factor limitation. Mol Cell, 50(1): 29–42
CrossRef
Pubmed
Google scholar
|
[34] |
Dowdle W E, Nyfeler B, Nagel J, Elling R A, Liu S, Triantafellow E, Menon S, Wang Z, Honda A, Pardee G, Cantwell J, Luu C, Cornella-Taracido I, Harrington E, Fekkes P, Lei H, Fang Q, Digan M E, Burdick D, Powers A F, Helliwell S B, D’Aquin S, Bastien J, Wang H, Wiederschain D, Kuerth J, Bergman P, Schwalb D, Thomas J, Ugwonali S, Harbinski F, Tallarico J, Wilson C J, Myer V E, Porter J A, Bussiere D E, Finan P M, Labow M A, Mao X, Hamann L G, Manning B D, Valdez R A, Nicholson T, Schirle M, Knapp M S, Keaney E P, Murphy L O (2014). Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat Cell Biol, 16(11): 1069–1079
CrossRef
Pubmed
Google scholar
|
[35] |
Druker B J, Tamura S, Buchdunger E, Ohno S, Segal G M, Fanning S, Zimmermann J, Lydon N B (1996). Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med, 2(5): 561–566
CrossRef
Pubmed
Google scholar
|
[36] |
Fan W, Nassiri A, Zhong Q (2011). Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc Natl Acad Sci USA, 108(19): 7769–7774
CrossRef
Pubmed
Google scholar
|
[37] |
Feng W, Huang S, Wu H, Zhang M (2007). Molecular basis of Bcl-xL’s target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of Beclin-1. J Mol Biol, 372(1): 223–235
CrossRef
Pubmed
Google scholar
|
[38] |
Fimia G M, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, Corazzari M, Fuoco C, Ucar A, Schwartz P, Gruss P, Piacentini M, Chowdhury K, Cecconi F (2007). Ambra1 regulates autophagy and development of the nervous system. Nature, 447(7148): 1121–1125
Pubmed
|
[39] |
Flores A M, Li L, Aneskievich B J (2004). Isolation and functional analysis of a keratinocyte-derived, ligand-regulated nuclear receptor comodulator. J Invest Dermatol, 123(6): 1092–1101
CrossRef
Pubmed
Google scholar
|
[40] |
Fogel A I, Dlouhy B J, Wang C, Ryu S W, Neutzner A, Hasson S A, Sideris D P, Abeliovich H, Youle R J (2013). Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy. Mol Cell Biol, 33(18): 3675–3688
CrossRef
Pubmed
Google scholar
|
[41] |
Furuya N, Yu J, Byfield M, Pattingre S, Levine B (2005). The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy, 1(1): 46–52
CrossRef
Pubmed
Google scholar
|
[42] |
Gannagé M, Dormann D, Albrecht R, Dengjel J, Torossi T, Rämer P C, Lee M, Strowig T, Arrey F, Conenello G, Pypaert M, Andersen J, García-Sastre A, Münz C (2009). Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes. Cell Host Microbe, 6(4): 367–380
CrossRef
Pubmed
Google scholar
|
[43] |
Gulati P, Gaspers L D, Dann S G, Joaquin M, Nobukuni T, Natt F, Kozma S C, Thomas A P, Thomas G (2008). Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell Metab, 7(5): 456–465
CrossRef
Pubmed
Google scholar
|
[44] |
Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T (2013). Autophagosomes form at ER-mitochondria contact sites. Nature, 495(7441): 389–393
CrossRef
Pubmed
Google scholar
|
[45] |
Harrison D E, Strong R, Sharp Z D, Nelson J F, Astle C M, Flurkey K, Nadon N L, Wilkinson J E, Frenkel K, Carter C S, Pahor M, Javors M A, Fernandez E, Miller R A (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 460(7253): 392–395
Pubmed
|
[46] |
Heenan E J, Vanhooke J L, Temple B R, Betts L, Sondek J E, Dohlman H G (2009). Structure and function of Vps15 in the endosomal G protein signaling pathway. Biochemistry, 48(27): 6390–6401
CrossRef
Pubmed
Google scholar
|
[47] |
Herman P K, Emr S D (1990). Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae. Mol Cell Biol, 10(12): 6742–6754
Pubmed
|
[48] |
Herman P K, Stack J H, DeModena J A, Emr S D (1991a). A novel protein kinase homolog essential for protein sorting to the yeast lysosome-like vacuole. Cell, 64(2): 425–437
CrossRef
Pubmed
Google scholar
|
[49] |
Herman P K, Stack J H, Emr S D (1991b). A genetic and structural analysis of the yeast Vps15 protein kinase: evidence for a direct role of Vps15p in vacuolar protein delivery. EMBO J, 10(13): 4049–4060
Pubmed
|
[50] |
Huang W, Choi W, Hu W, Mi N, Guo Q, Ma M, Liu M, Tian Y, Lu P, Wang F L, Deng H, Liu L, Gao N, Yu L, Shi Y (2012). Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein. Cell Res, 22(3): 473–489
CrossRef
Pubmed
Google scholar
|
[51] |
Hurley J H, Schulman B A (2014). Atomistic autophagy: the structures of cellular self-digestion. Cell, 157(2): 300–311
CrossRef
Pubmed
Google scholar
|
[52] |
Itakura E, Kishi C, Inoue K, Mizushima N (2008). Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell, 19(12): 5360–5372
CrossRef
Pubmed
Google scholar
|
[53] |
Itakura E, Kishi-Itakura C, Mizushima N (2012). The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell, 151(6): 1256–1269
CrossRef
Pubmed
Google scholar
|
[54] |
Itakura E, Mizushima N (2010). Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy, 6(6): 764–776
CrossRef
Pubmed
Google scholar
|
[55] |
Jaber N, Dou Z, Chen J S, Catanzaro J, Jiang Y P, Ballou L M, Selinger E, Ouyang X, Lin R Z, Zhang J, Zong W X (2012). Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. Proc Natl Acad Sci USA, 109(6): 2003–2008
CrossRef
Pubmed
Google scholar
|
[56] |
Jaeger P A, Pickford F, Sun C H, Lucin K M, Masliah E, Wyss-Coray T (2010). Regulation of amyloid precursor protein processing by the Beclin 1 complex. PLoS ONE, 5(6): e11102
CrossRef
Pubmed
Google scholar
|
[57] |
Joffre C, Dupont N, Hoa L, Gomez V, Pardo R, Gonçalves-Pimentel C, Achard P, Bettoun A, Meunier B, Bauvy C, Cascone I, Codogno P, Fanto M, Hergovich A, Camonis J (2015). The Pro-apoptotic STK38 Kinase Is a New Beclin1 Partner Positively Regulating Autophagy. Curr Biol,
CrossRef
Pubmed
Google scholar
|
[58] |
Kametaka S, Okano T, Ohsumi M, Ohsumi Y (1998). Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae. J Biol Chem, 273(35): 22284–22291
|
[59] |
Karsli-Uzunbas G, Guo J Y, Price S, Teng X, Laddha S V, Khor S, Kalaany N Y, Jacks T, Chan C S, Rabinowitz J D, White E (2014). Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov, 4(8): 914–927
CrossRef
Pubmed
Google scholar
|
[60] |
Kieffer C, Skalicky J J, Morita E, De Domenico I, Ward D M, Kaplan J, Sundquist W I (2008). Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding. Dev Cell, 15(1): 62–73
CrossRef
Pubmed
Google scholar
|
[61] |
Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (2001). Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep, 2(4): 330–335
CrossRef
Pubmed
Google scholar
|
[62] |
Kihara A, Noda T, Ishihara N, Ohsumi Y (2001). Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol, 152(3): 519–530
CrossRef
Pubmed
Google scholar
|
[63] |
Kim J, Kim Y C, Fang C, Russell R C, Kim J H, Fan W, Liu R, Zhong Q, Guan K L (2013). Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell, 152(1-2): 290–303
CrossRef
Pubmed
Google scholar
|
[64] |
Kim M S, Jeong E G, Ahn C H, Kim S S, Lee S H, Yoo N J (2008). Frameshift mutation of UVRAG, an autophagy-related gene, in gastric carcinomas with microsatellite instability. Hum Pathol, 39(7): 1059–1063
CrossRef
Pubmed
Google scholar
|
[65] |
Kim Y M, Jung C H, Seo M, Kim E K, Park J M, Bae S S, Kim D H (2015). mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation. Mol Cell, 57(2): 207–218
CrossRef
Pubmed
Google scholar
|
[66] |
Ku B, Woo J S, Liang C, Lee K H, Hong H S, e X, Kim K S, Jung J U, Oh B H (2008). Structural and biochemical bases for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. PLoS Pathog, 4(2): e25
CrossRef
Pubmed
Google scholar
|
[67] |
Kudchodkar S B, Levine B (2009). Viruses and autophagy. Rev Med Virol, 19(6): 359–378
CrossRef
Pubmed
Google scholar
|
[68] |
Kunz J B, Schwarz H, Mayer A (2004). Determination of four sequential stages during microautophagy in vitro. J Biol Chem, 279(11): 9987–9996
CrossRef
Pubmed
Google scholar
|
[69] |
Kyei G B, Dinkins C, Davis A S, Roberts E, Singh S B, Dong C, Wu L, Kominami E, Ueno T, Yamamoto A, Federico M, Panganiban A, Vergne I, Deretic V (2009). Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol, 186(2): 255–268
CrossRef
Pubmed
Google scholar
|
[70] |
Laddha S V, Ganesan S, Chan C S, White E (2014). Mutational landscape of the essential autophagy gene BECN1 in human cancers. Mol Cancer Res, 12(4): 485–490
CrossRef
Pubmed
Google scholar
|
[71] |
Levine B, Mizushima N, Virgin H W (2011). Autophagy in immunity and inflammation. Nature, 469(7330): 323–335
CrossRef
Pubmed
Google scholar
|
[72] |
Li X, He L, Che K H, Funderburk S F, Pan L, Pan N, Zhang M, Yue Z, Zhao Y (2012). Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG. Nat Commun, 3: 662
CrossRef
Pubmed
Google scholar
|
[73] |
Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh B H, Jung J U (2006). Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol, 8(7): 688–699
CrossRef
Pubmed
Google scholar
|
[74] |
Liang C, Lee J S, Inn K S, Gack M U, Li Q, Roberts E A, Vergne I, Deretic V, Feng P, Akazawa C, Jung J U (2008). Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol, 10(7): 776–787
CrossRef
Pubmed
Google scholar
|
[75] |
Liang Q, Chang B, Brulois K F, Castro K, Min C K, Rodgers M A, Shi M, Ge J, Feng P, Oh B H, Jung J U (2013). Kaposi’s sarcoma-associated herpesvirus K7 modulates Rubicon-mediated inhibition of autophagosome maturation. J Virol, 87(22): 12499–12503
CrossRef
Pubmed
Google scholar
|
[76] |
Liang Q, Seo G J, Choi Y J, Kwak M J, Ge J, Rodgers M A, Shi M, Leslie B J, Hopfner K P, Ha T, Oh B H, Jung J U (2014). Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host Microbe, 15(2): 228–238
CrossRef
Pubmed
Google scholar
|
[77] |
Liang X H, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999). Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature, 402(6762): 672–676
CrossRef
Pubmed
Google scholar
|
[78] |
Liang X H, Kleeman L K, Jiang H H, Gordon G, Goldman J E, Berry G, Herman B, Levine B (1998). Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol, 72(11): 8586–8596
Pubmed
|
[79] |
Lindmo K, Brech A, Finley K D, Gaumer S, Contamine D, Rusten T E, Stenmark H (2008). The PI 3-kinase regulator Vps15 is required for autophagic clearance of protein aggregates. Autophagy, 4(4): 500–506
CrossRef
Pubmed
Google scholar
|
[80] |
Liu J, Xia H, Kim M, Xu L, Li Y, Zhang L, Cai Y, Norberg H V, Zhang T, Furuya T, Jin M, Zhu Z, Wang H, Yu J, Li Y, Hao Y, Choi A, Ke H, Ma D, Yuan J (2011). Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell, 147(1): 223–234
CrossRef
Pubmed
Google scholar
|
[81] |
Lu J, He L, Behrends C, Araki M, Araki K, Jun Wang Q, Catanzaro J M, Friedman S L, Zong W X, Fiel M I, Li M, Yue Z (2014). NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity. Nat Commun, 5: 3920–3934
Pubmed
|
[82] |
Lucin K M, O’Brien C E, Bieri G, Czirr E, Mosher K I, Abbey R J, Mastroeni D F, Rogers J, Spencer B, Masliah E, Wyss-Coray T (2013). Microglial beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer’s disease. Neuron, 79(5): 873–886
CrossRef
Pubmed
Google scholar
|
[83] |
Ma B, Cao W, Li W, Gao C, Qi Z, Zhao Y, Du J, Xue H, Peng J, Wen J, Chen H, Ning Y, Huang L, Zhang H, Gao X, Yu L, Chen Y G (2014). Dapper1 promotes autophagy by enhancing the Beclin1-Vps34-Atg14L complex formation. Cell Res, 24(8): 912–924
CrossRef
Pubmed
Google scholar
|
[84] |
Maiuri M C, Criollo A, Tasdemir E, Vicencio J M, Tajeddine N, Hickman J A, Geneste O, Kroemer G (2007). BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L). Autophagy, 3(4): 374–376
CrossRef
Pubmed
Google scholar
|
[85] |
Maiuri M C, Le Toumelin G, Criollo A, Rain J C, Gautier F, Juin P, Tasdemir E, Pierron G, Troulinaki K, Tavernarakis N, Hickman J A, Geneste O, Kroemer G (2007). Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J, 26(10): 2527–2539
CrossRef
Pubmed
Google scholar
|
[86] |
Martell R E, Brooks D G, Wang Y, Wilcoxen K (2013). Discovery of novel drugs for promising targets. Clin Ther, 35(9): 1271–1281
CrossRef
Pubmed
Google scholar
|
[87] |
Massey A C, Kaushik S, Cuervo A M (2006). Lysosomal chat maintains the balance. Autophagy, 2(4): 325–327
CrossRef
Pubmed
Google scholar
|
[88] |
Mathew R, White E (2011). Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night. Curr Opin Genet Dev, 21(1): 113–119
CrossRef
Pubmed
Google scholar
|
[89] |
Matsunaga K, Morita E, Saitoh T, Akira S, Ktistakis N T, Izumi T, Noda T, Yoshimori T (2010). Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J Cell Biol, 190(4): 511–521
CrossRef
Pubmed
Google scholar
|
[90] |
Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T (2009). Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol, 11(4): 385–396
CrossRef
Pubmed
Google scholar
|
[91] |
McKnight N C, Jefferies H B, Alemu E A, Saunders R E, Howell M, Johansen T, Tooze S A (2012). Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. EMBO J, 31(8): 1931–1946
CrossRef
Pubmed
Google scholar
|
[92] |
McKnight N C, Zhong Y, Wold M S, Gong S, Phillips G R, Dou Z, Zhao Y, Heintz N, Zong W X, Yue Z (2014). Beclin 1 is required for neuron viability and regulates endosome pathways via the UVRAG-VPS34 complex. PLoS Genet, 10(10): e1004626
CrossRef
Pubmed
Google scholar
|
[93] |
Meléndez A, Tallóczy Z, Seaman M, Eskelinen E L, Hall D H, Levine B (2003). Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science, 301(5638): 1387–1391
CrossRef
Pubmed
Google scholar
|
[94] |
Michnick S W, Ear P H, Manderson E N, Remy I, Stefan E (2007). Universal strategies in research and drug discovery based on protein-fragment complementation assays. Nat Rev Drug Discov, 6(7): 569–582
CrossRef
Pubmed
Google scholar
|
[95] |
Miller S, Tavshanjian B, Oleksy A, Perisic O, Houseman B T, Shokat K M, Williams R L (2010). Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34. Science, 327(5973): 1638–1642
CrossRef
Pubmed
Google scholar
|
[96] |
Mizushima N, Yoshimori T, Ohsumi Y (2011). The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol, 27(1): 107–132
CrossRef
Pubmed
Google scholar
|
[97] |
Molejon M I, Ropolo A, Re A L, Boggio V, Vaccaro M I (2013). The VMP1-Beclin 1 interaction regulates autophagy induction. Sci Rep, 3: 1055
CrossRef
Pubmed
Google scholar
|
[98] |
Munson M J, Allen G F, Toth R, Campbell D G, Lucocq J M, Ganley I G (2015). mTOR activates the VPS34-UVRAG complex to regulate autolysosomal tubulation and cell survival. EMBO J, 34(17): 2272–2290
CrossRef
Pubmed
Google scholar
|
[99] |
Münz C (2011). Beclin-1 targeting for viral immune escape. Viruses, 3(7): 1166–1178
CrossRef
Pubmed
Google scholar
|
[100] |
Murray J T, Panaretou C, Stenmark H, Miaczynska M, Backer J M (2002). Role of Rab5 in the recruitment of hVps34/p150 to the early endosome. Traffic, 3(6): 416–427
CrossRef
Pubmed
Google scholar
|
[101] |
Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009). Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol, 10(7): 458–467
CrossRef
Pubmed
Google scholar
|
[102] |
Nassif M, Valenzuela V, Rojas-Rivera D, Vidal R, Matus S, Castillo K, Fuentealba Y, Kroemer G, Levine B, Hetz C (2014). Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis. Autophagy, 10(7): 1256–1271
CrossRef
Pubmed
Google scholar
|
[103] |
Nazio F, Strappazzon F, Antonioli M, Bielli P, Cianfanelli V, Bordi M, Gretzmeier C, Dengjel J, Piacentini M, Fimia G M, Cecconi F (2013). mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol, 15(4): 406–416
CrossRef
Pubmed
Google scholar
|
[104] |
Nemazanyy I, Montagnac G, Russell R C, Morzyglod L, Burnol A F, Guan K L, Pende M, Panasyuk G (2015). Class III PI3K regulates organismal glucose homeostasis by providing negative feedback on hepatic insulin signalling. Nat Commun, 6: 8283
CrossRef
Pubmed
Google scholar
|
[105] |
Noble C G, Dong J M, Manser E, Song H (2008). Bcl-xL and UVRAG cause a monomer-dimer switch in Beclin1. J Biol Chem, 283(38): 26274–26282
CrossRef
Pubmed
Google scholar
|
[106] |
Nobukuni T, Joaquin M, Roccio M, Dann S G, Kim S Y, Gulati P, Byfield M P, Backer J M, Natt F, Bos J L, Zwartkruis F J, Thomas G (2005). Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci USA, 102(40): 14238–14243
CrossRef
Pubmed
Google scholar
|
[107] |
Noda N N, Kobayashi T, Adachi W, Fujioka Y, Ohsumi Y, Inagaki F (2012). Structure of the novel C-terminal domain of vacuolar protein sorting 30/autophagy-related protein 6 and its specific role in autophagy. J Biol Chem, 287(20): 16256–16266
CrossRef
Pubmed
Google scholar
|
[108] |
Oberstein A, Jeffrey P D, Shi Y (2007). Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J Biol Chem, 282(17): 13123–13132
CrossRef
Pubmed
Google scholar
|
[109] |
Obita T, Saksena S, Ghazi-Tabatabai S, Gill D J, Perisic O, Emr S D, Williams R L (2007). Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4. Nature, 449(7163): 735–739
CrossRef
Pubmed
Google scholar
|
[110] |
Orvedahl A, Alexander D, Tallóczy Z, Sun Q, Wei Y, Zhang W, Burns D, Leib D A, Levine B (2007). HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe, 1(1): 23–35
CrossRef
Pubmed
Google scholar
|
[111] |
Panaretou C, Domin J, Cockcroft S, Waterfield M D (1997). Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150. Ptdins 3-kinase complex. J Biol Chem, 272(4): 2477–2485
CrossRef
Pubmed
Google scholar
|
[112] |
Pankiv S, Alemu E A, Brech A, Bruun J A, Lamark T, Overvatn A, Bjørkøy G, Johansen T (2010). FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. J Cell Biol, 188(2): 253–269
CrossRef
Pubmed
Google scholar
|
[113] |
Pasquier B, El-Ahmad Y, Filoche-Rommé B, Dureuil C, Fassy F, Abecassis P Y, Mathieu M, Bertrand T, Benard T, Barrière C, El Batti S, Letallec J P, Sonnefraud V, Brollo M, Delbarre L, Loyau V, Pilorge F, Bertin L, Richepin P, Arigon J, Labrosse J R, Clément J, Durand F, Combet R, Perraut P, Leroy V, Gay F, Lefrançois D, Bretin F, Marquette J P, Michot N, Caron A, Castell C, Schio L, McCort G, Goulaouic H, Garcia-Echeverria C, Ronan B (2015). Discovery of (2S)-8-((3R)-3-methylmorpholin-4-yl)-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors. J Med Chem, 58(1): 376–400
CrossRef
Pubmed
Google scholar
|
[114] |
Pattingre S, Tassa A, Qu X, Garuti R, Liang X H, Mizushima N, Packer M, Schneider M D, Levine B (2005). Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell, 122(6): 927–939
CrossRef
Pubmed
Google scholar
|
[115] |
Phillips S A, Barr V A, Haft D H, Taylor S I, Haft C R (2001). Identification and characterization of SNX15, a novel sorting nexin involved in protein trafficking. J Biol Chem, 276(7): 5074–5084
CrossRef
Pubmed
Google scholar
|
[116] |
Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger P A, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T (2008). The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest, 118(6): 2190–2199
Pubmed
|
[117] |
Polson H E, de Lartigue J, Rigden D J, Reedijk M, Urbé S, Clague M J, Tooze S A (2010). Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy, 6(4): 506–522
CrossRef
Pubmed
Google scholar
|
[118] |
Powis G, Bonjouklian R, Berggren M M, Gallegos A, Abraham R, Ashendel C, Zalkow L, Matter W F, Dodge J, Grindey G,
Pubmed
|
[119] |
Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen E L, Mizushima N, Ohsumi Y, Cattoretti G, Levine B (2003). Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest, 112(12): 1809–1820
CrossRef
Pubmed
Google scholar
|
[120] |
Ravikumar B, Imarisio S, Sarkar S, O’Kane C J, Rubinsztein D C (2008). Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J Cell Sci, 121(Pt 10): 1649–1660
CrossRef
Pubmed
Google scholar
|
[121] |
Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F, Bachelot M F, Lamberton A, Mathieu M, Bertrand T, Marquette J P, El-Ahmad Y, Filoche-Romme B, Schio L, Garcia-Echeverria C, Goulaouic H, Pasquier B (2014). A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol, 10(12): 1013–1019
CrossRef
Pubmed
Google scholar
|
[122] |
Ropolo A, Grasso D, Pardo R, Sacchetti M L, Archange C, Lo Re A, Seux M, Nowak J, Gonzalez C D, Iovanna J L, Vaccaro M I (2007). The pancreatitis-induced vacuole membrane protein 1 triggers autophagy in mammalian cells. J Biol Chem, 282(51): 37124–37133
CrossRef
Pubmed
Google scholar
|
[122a] |
Rostislavleva K, Soler N, Ohashi Y, Zhang L, Pardon E, Burke J E, Masson G R, Johnson C, Steyaert J, Ktistakis N T, Williams R L (2015). Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes. Science, 350: aac7365
|
[123] |
Schu P V, Takegawa K, Fry M J, Stack J H, Waterfield M D, Emr S D (1993). Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science, 260(5104): 88–91
CrossRef
Pubmed
Google scholar
|
[124] |
Seglen P O, Gordon P B (1982). 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA, 79(6): 1889–1892
CrossRef
Pubmed
Google scholar
|
[125] |
Shah N P, Tran C, Lee F Y, Chen P, Norris D, Sawyers C L (2004). Overriding imatinib resistance with a novel ABL kinase inhibitor. Science, 305(5682): 399–401
CrossRef
Pubmed
Google scholar
|
[126] |
Shi Y, Pellarin R, Fridy P C, Fernandez-Martinez J, Thompson M K, Li Y, Wang Q J, Sali A, Rout M P, Chait B T (2015). A strategy for dissecting the architectures of native macromolecular assemblies. Nature Methods, doi: 10.1038/nmeth.3617
|
[127] |
Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J (2006). Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J Biol Chem, 281(20): 14474–14485
CrossRef
Pubmed
Google scholar
|
[128] |
Shoji-Kawata S, Sumpter R, Leveno M, Campbell G R, Zou Z, Kinch L, Wilkins A D, Sun Q, Pallauf K, MacDuff D, Huerta C, Virgin H W, Helms J B, Eerland R, Tooze S A, Xavier R, Lenschow D J, Yamamoto A, King D, Lichtarge O, Grishin N V, Spector S A, Kaloyanova D V, Levine B (2013). Identification of a candidate therapeutic autophagy-inducing peptide. Nature, 494(7436): 201–206
CrossRef
Pubmed
Google scholar
|
[129] |
Siddhanta U, McIlroy J, Shah A, Zhang Y, Backer J M (1998). Distinct roles for the p110alpha and hVPS34 phosphatidylinositol 3′-kinases in vesicular trafficking, regulation of the actin cytoskeleton, and mitogenesis. J Cell Biol, 143(6): 1647–1659
CrossRef
Pubmed
Google scholar
|
[130] |
Simonsen A, Birkeland H C, Gillooly D J, Mizushima N, Kuma A, Yoshimori T, Slagsvold T, Brech A, Stenmark H (2004). Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes. J Cell Sci, 117(Pt 18): 4239–4251
CrossRef
Pubmed
Google scholar
|
[131] |
Sinha S, Colbert C L, Becker N, Wei Y, Levine B (2008). Molecular basis of the regulation of Beclin 1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11. Autophagy, 4(8): 989–997
CrossRef
Pubmed
Google scholar
|
[132] |
Slessareva J E, Routt S M, Temple B, Bankaitis V A, Dohlman H G (2006). Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosome. Cell, 126(1): 191–203
CrossRef
Pubmed
Google scholar
|
[133] |
Spencer B, Potkar R, Trejo M, Rockenstein E, Patrick C, Gindi R, Adame A, Wyss-Coray T, Masliah E (2009). Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson’s and Lewy body diseases. J Neurosci, 29(43): 13578–13588
CrossRef
Pubmed
Google scholar
|
[134] |
Stack J H, DeWald D B, Takegawa K, Emr S D (1995). Vesicle-mediated protein transport: regulatory interactions between the Vps15 protein kinase and the Vps34 PtdIns 3-kinase essential for protein sorting to the vacuole in yeast. J Cell Biol, 129(2): 321–334
CrossRef
Pubmed
Google scholar
|
[135] |
Stack J H, Herman P K, Schu P V, Emr S D (1993). A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole. EMBO J, 12(5): 2195–2204
Pubmed
|
[136] |
Starr T, Child R, Wehrly T D, Hansen B, Hwang S, López-Otin C, Virgin H W, Celli J (2012). Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle. Cell Host Microbe, 11(1): 33–45
CrossRef
Pubmed
Google scholar
|
[137] |
Strappazzon F, Nazio F, Corrado M, Cianfanelli V, Romagnoli A, Fimia G M, Campello S, Nardacci R, Piacentini M, Campanella M, Cecconi F (2014). AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ
Pubmed
|
[138] |
Strappazzon F, Vietri-Rudan M, Campello S, Nazio F, Florenzano F, Fimia G M, Piacentini M, Levine B, Cecconi F (2011). Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J, 30(7): 1195–1208
CrossRef
Pubmed
Google scholar
|
[139] |
Stuchell-Brereton M D, Skalicky J J, Kieffer C, Karren M A, Ghaffarian S, Sundquist W I (2007). ESCRT-III recognition by VPS4 ATPases. Nature, 449(7163): 740–744
CrossRef
Pubmed
Google scholar
|
[140] |
Su M, Mei Y, Sanishvili R, Levine B, Colbert C L, Sinha S (2014). Targeting γ-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy. J Biol Chem, 289(12): 8029–8040
CrossRef
Pubmed
Google scholar
|
[141] |
Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q (2008). Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc Natl Acad Sci USA, 105(49): 19211–19216
CrossRef
Pubmed
Google scholar
|
[142] |
Sun Q, Westphal W, Wong K N, Tan I, Zhong Q (2010). Rubicon controls endosome maturation as a Rab7 effector. Proc Natl Acad Sci USA, 107(45): 19338–19343
CrossRef
Pubmed
Google scholar
|
[143] |
Sun Q, Zhang J, Fan W, Wong K N, Ding X, Chen S, Zhong Q (2011). The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression. J Biol Chem, 286(1): 185–191
CrossRef
Pubmed
Google scholar
|
[144] |
Suetake T, Hayashi F, Yokoyama S (2015). Solution structure of MIT domain from mouse Nrbf2. (To be published)
|
[145] |
Suzuki K, Ohsumi Y (2007). Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett, 581(11): 2156–2161
CrossRef
Pubmed
Google scholar
|
[146] |
Taguchi-Atarashi N, Hamasaki M, Matsunaga K, Omori H, Ktistakis N T, Yoshimori T, Noda T (2010). Modulation of local PtdIns3P levels by the PI phosphatase MTMR3 regulates constitutive autophagy. Traffic, 11(4): 468–478
CrossRef
Pubmed
Google scholar
|
[147] |
Takahashi Y, Coppola D, Matsushita N, Cualing H D, Sun M, Sato Y, Liang C, Jung J U, Cheng J Q, Mulé J J, Pledger W J, Wang H G (2007). Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol, 9(10): 1142–1151
CrossRef
Pubmed
Google scholar
|
[148] |
Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S, Eishi Y, Hino O, Tanaka K, Mizushima N (2011). Autophagy-deficient mice develop multiple liver tumors. Genes Dev, 25(8): 795–800
CrossRef
Pubmed
Google scholar
|
[149] |
Takáts S, Pircs K, Nagy P, Varga Á, Kárpáti M, Hegedűs K, Kramer H, Kovács A L, Sass M, Juhász G (2014). Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila. Mol Biol Cell, 25(8): 1338–1354
CrossRef
Pubmed
Google scholar
|
[150] |
Terman A (1995). The effect of age on formation and elimination of autophagic vacuoles in mouse hepatocytes. Gerontology, 41(Suppl 2): 319–326
CrossRef
Pubmed
Google scholar
|
[151] |
Terman A, Gustafsson B, Brunk U T (2006). The lysosomal-mitochondrial axis theory of postmitotic aging and cell death. Chem Biol Interact, 163(1–2): 29–37
CrossRef
Pubmed
Google scholar
|
[152] |
Thoresen S B, Pedersen N M, Liestøl K, Stenmark H (2010). A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Exp Cell Res, 316(20): 3368–3378
CrossRef
Pubmed
Google scholar
|
[153] |
Uttenweiler A, Schwarz H, Neumann H, Mayer A (2007). The vacuolar transporter chaperone (VTC) complex is required for microautophagy. Mol Biol Cell, 18(1): 166–175
CrossRef
Pubmed
Google scholar
|
[154] |
Vakser I A (2014). Protein-protein docking: from interaction to interactome. Biophys J, 107(8): 1785–1793
CrossRef
Pubmed
Google scholar
|
[155] |
Van Humbeeck C, Cornelissen T, Hofkens H, Mandemakers W, Gevaert K, De Strooper B, Vandenberghe W (2011). Parkin interacts with Ambra1 to induce mitophagy. J Neurosci, 31(28): 10249–10261
CrossRef
Pubmed
Google scholar
|
[156] |
Vergne I, Roberts E, Elmaoued R A, Tosch V, Delgado M A, Proikas-Cezanne T, Laporte J, Deretic V (2009). Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy. EMBO J, 28(15): 2244–2258
CrossRef
Pubmed
Google scholar
|
[157] |
Vlahos C J, Matter W F, Hui K Y, Brown R F (1994). A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem, 269(7): 5241–5248
Pubmed
|
[158] |
Volinia S, Dhand R, Vanhaesebroeck B, MacDougall L K, Stein R, Zvelebil M J, Domin J, Panaretou C, Waterfield M D (1995). A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J, 14(14): 3339–3348
Pubmed
|
[159] |
Wei Y, Pattingre S, Sinha S, Bassik M, Levine B (2008). JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell, 30(6): 678–688
CrossRef
Pubmed
Google scholar
|
[160] |
Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G, Kinch L, Koduru P, Christudass C S, Veltri R W, Grishin N V, Peyton M, Minna J, Bhagat G, Levine B (2013). EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell, 154(6): 1269–1284
CrossRef
Pubmed
Google scholar
|
[161] |
Wu Y T, Tan H L, Shui G, Bauvy C, Huang Q, Wenk M R, Ong C N, Codogno P, Shen H M (2010). Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem, 285(14): 10850–10861
CrossRef
Pubmed
Google scholar
|
[162] |
Xu L, Salloum D, Medlin P S, Saqcena M, Yellen P, Perrella B, Foster D A (2011). Phospholipase D mediates nutrient input to mammalian target of rapamycin complex 1 (mTORC1). J Biol Chem, 286(29): 25477–25486
CrossRef
Pubmed
Google scholar
|
[163] |
Yan Y, Flinn R J, Wu H, Schnur R S, Backer J M (2009). hVps15, but not Ca2+/CaM, is required for the activity and regulation of hVps34 in mammalian cells. Biochem J, 417(3): 747–755
CrossRef
Pubmed
Google scholar
|
[164] |
Yang C S, Lee J S, Rodgers M, Min C K, Lee J Y, Kim H J, Lee K H, Kim C J, Oh B, Zandi E, Yue Z, Kramnik I, Liang C, Jung J U (2012a). Autophagy protein Rubicon mediates phagocytic NADPH oxidase activation in response to microbial infection or TLR stimulation. Cell Host Microbe, 11(3): 264–276
CrossRef
Pubmed
Google scholar
|
[165] |
Yang C S, Rodgers M, Min C K, Lee J S, Kingeter L, Lee J Y, Jong A, Kramnik I, Lin X, Jung J U (2012b). The autophagy regulator Rubicon is a feedback inhibitor of CARD9-mediated host innate immunity. Cell Host Microbe, 11(3): 277–289
CrossRef
Pubmed
Google scholar
|
[166] |
Yasumo H, Masuda N, Furusawa T, Tsukamoto T, Sadano H, Osumi T (2000). Nuclear receptor binding factor-2 (NRBF-2), a possible gene activator protein interacting with nuclear hormone receptors. Biochim Biophys Acta, 1490(1-2): 189–197
CrossRef
Pubmed
Google scholar
|
[167] |
Yoon M S, Du G, Backer J M, Frohman M A, Chen J (2011). Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway. J Cell Biol, 195(3): 435–447
CrossRef
Pubmed
Google scholar
|
[168] |
Yue Z, Jin S, Yang C, Levine A J, Heintz N (2003). Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA, 100(25): 15077–15082
CrossRef
Pubmed
Google scholar
|
[169] |
Zalckvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, Eisenstein M, Sabanay H, Pinkas-Kramarski R, Kimchi A (2009). DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO Rep, 10(3): 285–292
CrossRef
Pubmed
Google scholar
|
[170] |
Zhong Y, Morris D H, Jin L, Patel M S, Karunakaran S K, Fu Y J, Matuszak E A, Weiss H L, Chait B T, Wang Q J (2014). Nrbf2 protein suppresses autophagy by modulating Atg14L protein-containing Beclin 1-Vps34 complex architecture and reducing intracellular phosphatidylinositol-3 phosphate levels. J Biol Chem, 289(38): 26021–26037
CrossRef
Pubmed
Google scholar
|
[171] |
Zhong Y, Wang Q J, Li X, Yan Y, Backer J M, Chait B T, Heintz N, Yue Z (2009). Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol, 11(4): 468–476
CrossRef
Pubmed
Google scholar
|
[172] |
Zhou D, Spector S A (2008). Human immunodeficiency virus type-1 infection inhibits autophagy. AIDS, 22(6): 695–699
CrossRef
Pubmed
Google scholar
|
[173] |
Zhou X, Takatoh J, Wang F (2011). The mammalian class 3 PI3K (PIK3C3) is required for early embryogenesis and cell proliferation. PLoS ONE, 6(1): e16358
CrossRef
Pubmed
Google scholar
|
/
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