Mutation analysis of large tumor suppressor genes LATS1 and LATS2 supports a tumor suppressor role in human cancer
Tian Yu, John Bachman, Zhi-Chun Lai
Mutation analysis of large tumor suppressor genes LATS1 and LATS2 supports a tumor suppressor role in human cancer
In recent years, human cancer genome projects provide unprecedented opportunities for the discovery of cancer genes and signaling pathways that contribute to tumor development. While numerous gene mutations can be identified from each cancer genome, what these mutations mean for cancer is a challenging question to address, especially for those from less understood putative new cancer genes. As a powerful approach, in silico bioinformatics analysis could efficiently sort out mutations that are predicted to damage gene function. Such an analysis of human large tumor suppressor genes, LATS1 and LATS2, has been carried out and the results support a role of hLATS1//2 as negative growth regulators and tumor suppressors.
LATS1 & LATS2 / hippo signaling / cancer genome / human cancer
[1] |
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods7: 248-249
CrossRef
Google scholar
|
[2] |
Choi Y, Sims GE, Murphy S, Miller JR, Chan AP (2012) Predicting the functional effect of amino acid substitutions and indels. PloS One7: e46688
CrossRef
Google scholar
|
[3] |
Endicott JA, Noble ME, Johnson LN (2012) The structural basis for control of eukaryotic protein kinases. Annu Rev Biochem81: 587-613
CrossRef
Google scholar
|
[4] |
Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J9: 576-596
|
[5] |
Harvey KF, Zhang X, Thomas DM (2013) The Hippo pathway and human cancer. Nat Rev Cancer13: 246-257
CrossRef
Google scholar
|
[6] |
Hergovich A, Stegert MR, Schmitz D, Hemmings BA (2006) NDR kinases regulate essential cell processes from yeast to humans. Nat Rev Mol Cell Biol7: 253-264
CrossRef
Google scholar
|
[7] |
Ho LL, Wei X, Shimizu T, Lai ZC (2010) Mob as tumor suppressor is activated at the cell membrane to control tissue growth and organ size in Drosophila. Dev Biol337: 274-283
CrossRef
Google scholar
|
[8] |
Hornbeck PV, Kornhauser JM, Tkachev S, Zhang B, Skrzypek E, Murray B, Latham V, Sullivan M (2012) PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res40: D261-D270
CrossRef
Google scholar
|
[9] |
Leonard TA, Różycki B, Saidi LF, Hummer G, Hurley JH (2011) Crystal structure and allosteric activation of protein kinase C βII. Cell144: 55-66
CrossRef
Google scholar
|
[10] |
Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, Akatsuka S, Horio Y, Hida T, Kondo Y, Toyokuni S, Osada H, Sekido Y (2011) LATS2 is a tumor suppressor gene of malignant mesothelioma. Cancer Res71: 873-883
CrossRef
Google scholar
|
[11] |
Ng PC, Henikoff S (2003) SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res31: 3812-3814
CrossRef
Google scholar
|
[12] |
Okada N, Yabuta N, Suzuki H, Aylon Y, Oren M, Nojima H (2011) A novel Chk1/2–Lats2–14-3-3 signaling pathway regulates P-body formation in response to UV damage. J Cell Sci124: 57-67
CrossRef
Google scholar
|
[13] |
Paramasivam M, Sarkeshik A, Yates JR, Fernandes MJ, McCollum D (2011) Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor. Mol Biol Cell22: 3725-3733
CrossRef
Google scholar
|
[14] |
Reva B, Antipin Y, Sander C (2011) Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res39: e118
CrossRef
Google scholar
|
[15] |
Visser S, Yang X (2010) LATS tumor suppressor: a new governor of cellular homeostasis. Cell Cycle9: 3892-3903
CrossRef
Google scholar
|
[16] |
Wei X, Shimizu T, Lai ZC (2007) Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in Drosophila. EMBO J26: 1772-1781
CrossRef
Google scholar
|
[17] |
Xiao L, Chen Y, Ji M, Dong J (2011) KIBRA regulates Hippo signaling activity via interactions with large tumor suppressor kinases. J Biol Chem286: 7788-7796
CrossRef
Google scholar
|
[18] |
Yabuta N, Mukai S, Okada N, Aylon Y, Nojima H (2011) The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis. Cell Cycle10: 2724-2736
CrossRef
Google scholar
|
[19] |
Yin F, Yu J, Zheng Y, Chen Q, Zhang N, Pan D (2013) Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell154: 1342-1355
CrossRef
Google scholar
|
[20] |
Yu FX, Guan KL (2013) The Hippo pathway: regulators and regulations. Genes Dev27: 355-371
CrossRef
Google scholar
|
[21] |
Yu T, Bachman J, Lai ZC (2013) Evidence for a tumor suppressor role for the large tumor suppressor genes LATS1 and LATS2 in human cancer. Genetics195: 1193-1196
CrossRef
Google scholar
|
[22] |
Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai ZC, Guan KL (2007) Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev2747-2761
CrossRef
Google scholar
|
/
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