Toward an understanding of cancer-associated ribosomal protein mutations

Abstract

Ribosomal proteins (RPs) are essential structural and functional components of the ribosome, and their disruption during embryogenesis generally results in embryonic lethality. Nevertheless, cancer genomes frequently harbor somatic missense mutations and gene deletions in RP genes in patterns that suggest selective advantages, often linked to inactivation of the tumor suppressor protein p53 pathway. This review discusses the landscape of RP mutations in cancer and their mechanistic consequences. RP mutations are detected across multiple malignancies, including glioblastoma, melanoma, T-cell acute lymphoblastic leukemia, as well as in congenital ribosomopathies, such as Diamond-Blackfan anemia, which confer an elevated lifetime risk of developing cancer. Cancer-associated RP mutations disturb ribosome homeostasis, compromise translational fidelity, and trigger proteotoxic and ribosomal stress, yet without halting tumor growth. Some RP mutants occupy structurally sensitive positions within the ribosome, altering mRNA selectivity and quality control. In turn, cancer cells may adapt through compensatory mechanisms, including the upregulation of RP paralogs, activation of proteostasis regulators, and rewiring of stress response pathways. Rather than a loss-of-function event, an RP mutation may create a persistent ribosomal disequilibrium that fundamentally alters cellular functions. Such changes in a cancer cell could generate interesting therapeutic vulnerabilities and targets, such as dependence on stress signaling, proteasome activity, or RP paralog expression.

Keywords

Ribosome biogenesis / Ribosomal protein / p53 / Cancer / Ribosomal stress

References

[1] Shore D, Albert B. Ribosome biogenesis and the cellular energy economy. Curr Biol. 2022; 32(12):R611-R617. doi: 10.1016/j.cub.2022.04.083

[2] Baßler J, Hurt E.Eukaryotic ribosome assembly. Annu Rev Biochem. 2019;88:281-306. doi: 10.1146/annurev-biochem-013118-110817

[3] Wool IG. The structure and function of eukaryotic ribosomes. Annu Rev Biochem. 1979; 48:719-754. doi: 10.1146/annurev.bi.48.070179.003443

[4] Melnikov S, Ben-Shem A, Garreau de Loubresse N, Jenner L, Yusupova G, Yusupov M. One core, two shells: Bacterial and eukaryotic ribosomes. Nat Struct Mol Biol. 2012; 19(6):560-567. doi: 10.1038/nsmb.2313

[5] Khatter H, Myasnikov AG, Natchiar SK, Klaholz BP. Structure of the human 80S ribosome. Nature. 2015; 520(7549):640-645. doi: 10.1038/nature14427

[6] Ni C, Buszczak M. The homeostatic regulation of ribosome biogenesis. Semin Cell Dev Biol. 2023; 136:13-26. doi: 10.1016/j.semcdb.2022.03.043

[7] Perry RP.Balanced production of ribosomal proteins. Gene. 2007; 401(1-2):1-3. doi: 10.1016/j.gene.2007.07.007

[8] Albert B, Knight B, Merwin J, et al. A molecular titration system coordinates ribosomal protein gene transcription with ribosomal RNA synthesis. Mol Cell. 2016; 64(4):720-733. doi: 10.1016/j.molcel.2016.10.003

[9] Chunduri NK, Menges P, Zhang X, et al. Systems approaches identify the consequences of monosomy in somatic human cells. Nat Commun. 2021; 12(1):5576. doi: 10.1038/s41467-021-25288-x

[10] Donnelly N, Passerini V, Dürrbaum M, Stingele S, Storchová Z. HSF1 deficiency and impaired HSP90-dependent protein folding are hallmarks of aneuploid human cells. EMBO J. 2014; 33(20):2374-2387. doi: 10.15252/embj.201488648

[11] Sulima SO, Kampen KR, Vereecke S, et al. Ribosomal lesions promote oncogenic mutagenesis. Cancer Res. 2019; 79(2):320-327. doi: 10.1158/0008-5472.can-18-1987

[12] Panda A, Yadav A, Yeerna H, et al. Tissue- and development- stage-specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples. Nucleic Acids Res. 2020; 48(13):7079-7098. doi: 10.1093/nar/gkaa485

[13] Ajore R, Raiser D, McConkey M, et al. Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations. EMBO Mol Med. 2017; 9(4):498-507. doi: 10.15252/emmm.201606660

[14] Sulima SO, Hofman IJF,De Keersmaecker K, Dinman JD. How ribosomes translate cancer. Cancer Discov. 2017; 7(10):1069-1087. doi: 10.1158/2159-8290.CD-17-0550

[15] Kampen KR, Sulima SO, Vereecke S,De Keersmaecker K. Hallmarks of ribosomopathies. Nucleic Acids Res. 2020; 48(3):1013-1028. doi: 10.1093/nar/gkz637

[16] Warner JR, McIntosh KB. How common are extraribosomal functions of ribosomal proteins? Mol Cell. 2009; 34(1):3-11. doi: 10.1016/j.molcel.2009.03.006

[17] Ramalho S, Dopler A, Faller WJ. Ribosome specialization in cancer: A spotlight on ribosomal proteins. NAR Cancer. 2024; 6(3):zcae029. doi: 10.1093/narcan/zcae029

[18] Jiao L, Liu Y, Yu XY, et al. Ribosome biogenesis in disease: New players and therapeutic targets. Signal Transduct Target Ther. 2023; 8(1):15. doi: 10.1038/s41392-022-01285-4

[19] Klinge S, Woolford JL.Ribosome assembly coming into focus. Nat Rev Mol Cell Biol. 2019; 20(2):116-131. doi: 10.1038/s41580-018-0078-y

[20] Ni C, Buszczak M. Ribosome biogenesis and function in development and disease. Development. 2023; 150(5):dev201187. doi: 10.1242/dev.201187

[21] Shore D, Zencir S, Albert B. Transcriptional control of ribosome biogenesis in yeast: Links to growth and stress signals. Biochem Soc Trans. 2021; 49(4):1589-1599. doi: 10.1042/BST20201136

[22] Jäkel S, Görlich D. Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. EMBO J. 1998; 17(15):4491-4502. doi: 10.1093/emboj/17.15.4491

[23] Kressler D, Bange G, Ogawa Y, et al. Synchronizing nuclear import of ribosomal proteins with ribosome assembly. Science. 2012; 338(6107):666-671. doi: 10.1126/science.1226960

[24] Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: Mechanisms and biological targets. Cell. 2009; 136(4):731-745. doi: 10.1016/j.cell.2009.01.042

[25] Ramakrishnan V. Ribosome structure and the mechanism of translation. Cell. 2002; 108(4):557-572. doi: 10.1016/s0092-8674(02)00619-0

[26] Fox GE. Origin and evolution of the ribosome. Cold Spring Harb Perspect Biol. 2010; 2(9):a003483. doi: 10.1101/cshperspect.a003483

[27] Ferreira-Cerca S, Pöll G, Gleizes PE, Tschochner H, Milkereit P. Roles of eukaryotic ribosomal proteins in maturation and transport of pre-18S rRNA and ribosome function. Mol Cell. 2005; 20(2):263-275. doi: 10.1016/j.molcel.2005.09.005

[28] Robledo S, Idol RA, Crimmins DL, Ladenson JH, Mason PJ, Bessler M. The role of human ribosomal proteins in the maturation of rRNA and ribosome production. RNA. 2008; 14(9):1918-1929. doi: 10.1261/rna.1132008

[29] O’Donohue MF, Choesmel V, Faubladier M, Fichant G, Gleizes PE. Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits. J Cell Biol. 2010; 190(5):853-866. doi: 10.1083/jcb.201005117

[30] Nicolas E, Parisot P, Pinto-Monteiro C, De Walque R, De Vleeschouwer C, Lafontaine DLJ. Involvement of human ribosomal proteins in nucleolar structure and p53- dependent nucleolar stress. Nat Commun. 2016;7:11390. doi: 10.1038/ncomms11390

[31] Badertscher L, Wild T, Montellese C, et al. Genome-wide RNAi screening identifies protein modules required for 40s subunit synthesis in human cells. Cell Rep. 2015; 13(12):2879-2891. doi: 10.1016/j.celrep.2015.11.061

[32] Dörner K, Badertscher L, Horváth B, et al. Genome-wide RNAi screen identifies novel players in human 60S subunit biogenesis including key enzymes of polyamine metabolism. Nucleic Acids Res. 2022; 50(5):2872-2888. doi: 10.1093/nar/gkac072

[33] Lam YW, Lamond AI, Mann M, Andersen JS. Analysis of nucleolar protein dynamics reveals the nuclear degradation of ribosomal proteins. Curr Biol. 2007; 17(9):749-760. doi: 10.1016/j.cub.2007.03.064

[34] Andersen JS, Lam YW, Leung AKL, et al. Nucleolar proteome dynamics. Nature. 2005; 433(7021):77-83. doi: 10.1038/nature03207

[35] Sung MK, Porras-Yakushi TR, Reitsma JM, et al. A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins. Elife. 2016;5:e19105. doi: 10.7554/eLife.19105

[36] Schubert U, Antón LC, Gibbs J, Norbury CC, Yewdell JW, Bennink JR. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature. 2000; 404(6779):770-774. doi: 10.1038/35008096

[37] Ju D, Li L, Xie Y. Homeostatic regulation of ribosomal proteins by ubiquitin-independent cotranslational degradation. Proc Natl Acad Sci U S A. 2023; 120(30):e2306152120. doi: 10.1073/pnas.2306152120

[38] Granneman S, Tollervey D. Building ribosomes: Even more expensive than expected? Curr Biol. 2007; 17(11):R415-R417. doi: 10.1016/j.cub.2007.04.011

[39] Pelletier J, Thomas G, Volarević S. Ribosome biogenesis in cancer: New players and therapeutic avenues. Nat Rev Cancer. 2018; 18(1):51-63. doi: 10.1038/nrc.2017.104

[40] Bywater MJ, Pearson RB, McArthur GA, Hannan RD. Dysregulation of the basal RNA polymerase transcription apparatus in cancer. Nat Rev Cancer. 2013; 13(5):299-314. doi: 10.1038/nrc3496

[41] Ballester LY, Boghani Z, Baskin DS, et al. Creutzfeldt astrocytes may be seen in IDH-wildtype glioblastoma and retain expression of DNA repair and chromatin binding proteins. Brain Pathol. 2018; 28(6):1012-1019. doi: 10.1111/bpa.12604

[42] Galbraith K, Snuderl M.Molecular pathology of gliomas. Clin Lab Med. 2024; 44(2):149-159. doi: 10.1016/j.cll.2023.08.009

[43] Zhao S, Chen L, Zang Y, et al. Endometrial cancer in lynch syndrome. Int J Cancer. 2022; 150(1):7-17. doi: 10.1002/ijc.33763

[44] Cicenas J, Kvederaviciute K, Meskinyte I, Meskinyte- Kausiliene E, Skeberdyte A, Cicenas J. KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 mutations in pancreatic cancer. Cancers (Basel). 2017; 9(5):42. doi: 10.3390/cancers9050042

[45] Draptchinskaia N, Gustavsson P, Andersson B, et al. The gene encoding ribosomal protein S19 is mutated in Diamond- Blackfan anaemia. Nat Genet. 1999; 21(2):169-175. doi: 10.1038/5951

[46] Gazda HT, Sheen MR, Vlachos A, et al. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008; 83(6):769-780. doi: 10.1016/j.ajhg.2008.11.004

[47] Farrar JE, Vlachos A, Atsidaftos E, et al. Ribosomal protein gene deletions in Diamond-Blackfan anemia. Blood. 2011; 118(26):6943-6951. doi: 10.1182/blood-2011-08-375170

[48] Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM. Incidence of neoplasia in Diamond Blackfan anemia: A report from the diamond blackfan anemia registry. Blood. 2012; 119(16):3815-3819. doi: 10.1182/blood-2011-08-375972

[49] Farley-Barnes KI, Ogawa LM, Baserga SJ.Ribosomopathies: Old concepts, new controversies. Trends Genet. 2019; 35(10):754-767. doi: 10.1016/j.tig.2019.07.004

[50] Narla A, Ebert BL. Ribosomopathies: Human disorders of ribosome dysfunction. Blood. 2010; 115(16):3196-3205. doi: 10.1182/blood-2009-10-178129

[51] De Keersmaecker K, Atak ZK, Li N, et al. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet. 2013; 45(2):186-190. doi: 10.1038/ng.2508

[52] Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013; 502(7471):333-339. doi: 10.1038/nature12634

[53] Nagarajan N, Bertrand D, Hillmer AM, et al. Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol. 2012; 13(12):R115. doi: 10.1186/gb-2012-13-12-r115

[54] Novetsky AP, Zighelboim I, Thompson DM, Powell MA, Mutch DG, Goodfellow PJ. Frequent mutations in the RPL22 gene and its clinical and functional implications. Gynecol Oncol. 2013; 128(3):470-474. doi: 10.1016/j.ygyno.2012.10.026

[55] Lawrence MS, Stojanov P, Mermel CH, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature. 2014; 505(7484):495-501. doi: 10.1038/nature12912

[56] Oršolić I, Bursać S, Jurada D, et al. Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2/p53-mediated ribosome biogenesis checkpoint. Oncogene. 2020; 39(17):3443-3457. doi: 10.1038/s41388-020-1231-6

[57] Fancello L, Kampen KR, Hofman IJF, Verbeeck J, De Keersmaecker K. The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types. Oncotarget. 2017; 8(9):14462-14478. doi: 10.18632/oncotarget.14895

[58] Weinstein HNW, Hu K, Fish L, et al. RPL 22 is a tumor suppressor in MSI-high cancers and a splicing regulator of MDM4. Cell Rep. 2024; 43(8):114622. doi: 10.1016/j.celrep.2024.114622

[59] Rao S, Lee SY, Gutierrez A, et al. Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood. 2012; 120(18):3764-3773. doi: 10.1182/blood-2012-03-415349

[60] Ljungström V, Cortese D, Young E, et al. Whole-exome sequencing in relapsing chronic lymphocytic leukemia: Clinical impact of recurrent RPS15 mutations. Blood. 2016; 127(8):1007-1016. doi: 10.1182/blood-2015-10-674572

[61] Nieminen TT, O’Donohue MF, Wu Y, et al. Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency. Gastroenterology. 2014; 147(3):595-598.e5. doi: 10.1053/j.gastro.2014.06.009

[62] Amiot J, Gubeljak L, Fontaine A, et al. New RPS20 gene variant in colorectal cancer diagnosis: Insight from a large series of patients. Fam Cancer. 2025; 24(1):22. doi: 10.1007/s10689-025-00446-y

[63] Dutton-Regester K, Gartner JJ, Emmanuel R, et al. A highly recurrent RPS27 5’UTR mutation in melanoma. Oncotarget. 2014; 5(10):2912-2917. doi: 10.18632/oncotarget.2048

[64] Genuth NR, Barna M. The discovery of ribosome heterogeneity and its implications for gene regulation and organismal life. Mol Cell. 2018; 71(3):364-374. doi: 10.1016/j.molcel.2018.07.018

[65] Slavov N, Semrau S, Airoldi E, Budnik B, Van Oudenaarden A. Differential stoichiometry among core ribosomal proteins. Cell Rep. 2015; 13(5):865-873. doi: 10.1016/j.celrep.2015.09.056

[66] Shi Z, Fujii K, Kovary KM, et al. Heterogeneous ribosomes preferentially translate distinct subpools of mRNAs genome- wide. Mol Cell. 2017; 67(1):71-83.e7. doi: 10.1016/j.molcel.2017.05.021

[67] Simsek D, Tiu GC, Flynn RA, et al. The mammalian ribo- interactome reveals ribosome functional diversity and heterogeneity. Cell. 2017; 169(6):1051-1065.e18. doi: 10.1016/j.cell.2017.05.022

[68] Kyei-Baffour ES, Lin QC, Alkan F, Faller WJ. High- throughput approaches for the identification of ribosome heterogeneity. Philos Trans R Soc Lond B Biol Sci. 2025; 380(1921):20230381. doi: 10.1098/rstb.2023.0381

[69] Gilbert WV. Functional specialization of ribosomes? Trends Biochem Sci. 2011; 36(3):127-132. doi: 10.1016/j.tibs.2010.12.002

[70] Ferretti MB, Karbstein K. Does functional specialization of ribosomes really exist? RNA. 2019; 25(5):521-538. doi: 10.1261/rna.069823.118

[71] Li H, Huo Y, He X, et al. A male germ-cell-specific ribosome controls male fertility. Nature. 2022; 612(7941):725-731. doi: 10.1038/s41586-022-05508-0

[72] Milenkovic I, Novoa EM. Ribosomal protein paralogues in ribosome specialization. Philos Trans R Soc Lond B Biol Sci. 2025; 380(1921):20230387. doi: 10.1098/rstb.2023.0387

[73] Ebert BL, Pretz J, Bosco J, et al. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature. 2008; 451(7176):335-339. doi: 10.1038/nature06494

[74] Larionova TD, Bastola S, Aksinina TE, et al. Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells. Nat Cell Biol. 2022; 24(10):1541-1557. doi: 10.1038/s41556-022-00994-w

[75] Kulkarni S, Dolezal JM, Wang H, et al. Ribosomopathy- like properties of murine and human cancers. PLoS One. 2017; 12(8):e0182705. doi: 10.1371/journal.pone.0182705

[76] Luan Y, Tang N, Yang J, et al. Deficiency of ribosomal proteins reshapes the transcriptional and translational landscape in human cells. Nucleic Acids Res. 2022; 50(12):6601-6617. doi: 10.1093/nar/gkac053

[77] Guimaraes JC, Zavolan M. Patterns of ribosomal protein expression specify normal and malignant human cells. Genome Biol. 2016; 17(1):236. doi: 10.1186/s13059-016-1104-z

[78] Dolezal JM, Dash AP, Prochownik EV. Diagnostic and prognostic implications of ribosomal protein transcript expression patterns in human cancers. BMC Cancer. 2018; 18(1):275. doi: 10.1186/s12885-018-4178-z

[79] Wang H, Zhao LN, Li KZ, Ling R, Li XJ, Wang L. Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer. BMC Cancer. 2006;6:91. doi: 10.1186/1471-2407-6-91

[80] Ebright RY, Lee S, Wittner BS, et al. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis. Science. 2020; 367(6485):1468-1473. doi: 10.1126/science.aay0939

[81] Fuentes P, Pelletier J, Gentilella A. Decoding ribosome complexity: Role of ribosomal proteins in cancer and disease. NAR Cancer. 2024; 6(3):zcae032. doi: 10.1093/narcan/zcae032

[82] Lafita-Navarro MC, Conacci-Sorrell M. Nucleolar stress: From development to cancer. Semin Cell Dev Biol. 2023; 136:64-74. doi: 10.1016/j.semcdb.2022.04.001

[83] De Las Heras-Rubio A, Perucho L, Paciucci R, Vilardell J, LLeonart ME. Ribosomal proteins as novel players in tumorigenesis. Cancer Metastasis Rev. 2014; 33(1):115-141. doi: 10.1007/s10555-013-9460-6

[84] Sjövall D, Ghosh S, Fernandez-Fuentes N, et al. Defective ribosome assembly impairs leukemia progression in a murine model of acute myeloid leukemia. Cell Rep. 2024; 43(11):114864. doi: 10.1016/j.celrep.2024.114864

[85] Caruso M, De Keersmaecker K. Ribosome specialization by cancer-associated ribosomal protein mutations: Progress made and open questions. Philos Trans R Soc Lond B Biol Sci. 2025; 380(1921):20230380. doi: 10.1098/rstb.2023.0380

[86] Mills EW, Green R.Ribosomopathies: There’s strength in numbers. Science. 2017; 358(6363):eaan2755. doi: 10.1126/science.aan2755

[87] Khajuria RK, Munschauer M, Ulirsch JC, et al. Ribosome levels selectively regulate translation and lineage commitment in human hematopoiesis. Cell. 2018; 173(1):90-103.e19. doi: 10.1016/j.cell.2018.02.036

[88] Kessel R, Vlachos A, Lipton JM.Ribosomopathy association with colorectal cancer. Gastroenterology. 2015; 148(1):258. doi: 10.1053/j.gastro.2014.08.046

[89] Volarevic S, Stewart MJ, Ledermann B, et al.Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6. Science. 2000; 288(5473):2045-2047. doi: 10.1126/science.288.5473.2045

[90] Pestov DG, Strezoska Z, Lau LF. Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: Effects of nucleolar protein Bop1 on G(1)/S transition. Mol Cell Biol. 2001; 21(13):4246-4255. doi: 10.1128/mcb.21.13.4246-4255.2001

[91] Hölzel M, Orban M, Hochstatter J, et al. Defects in 18 S or 28 S rRNA processing activate the p53 pathway. J Biol Chem. 2010; 285(9):6364-6370. doi: 10.1074/jbc.M109.054734

[92] Macias E, Jin A, Deisenroth C, et al. An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 interaction. Cancer Cell. 2010; 18(3):231-243. doi: 10.1016/j.ccr.2010.08.007

[93] Morcelle C, Menoyo S, Morón-Duran FD, et al. Oncogenic MYC induces the impaired ribosome biogenesis checkpoint and stabilizes p53 independent of increased ribosome content. Cancer Res. 2019; 79(17):4348-4359. doi: 10.1158/0008-5472.can-18-2718

[94] Liu Y, Su Z, Tavana O, Gu W. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell. 2024; 42(6):946-967. doi: 10.1016/j.ccell.2024.04.009

[95] Tanikawa C, Zhang YZ, Yamamoto R, et al. The transcriptional landscape of p53 signalling pathway. EBioMedicine. 2017; 20:109-119. doi: 10.1016/j.ebiom.2017.05.017

[96] Andrysik Z, Galbraith MD, Guarnieri AL, et al. Identification of a core TP53 transcriptional program with highly distributed tumor suppressive activity. Genome Res. 2017; 27(10):1645-1657. doi: 10.1101/gr.220533.117

[97] Liao H, Gaur A, Mauvais C, Denicourt C. p53 induces a survival transcriptional response after nucleolar stress. Mol Biol Cell. 2021; 32(20):ar3. doi: 10.1091/mbc.E21-05-0251

[98] McGirr T, Onar O, Jafarnejad SM. Dysregulated ribosome quality control in human diseases. FEBS J. 2025; 292(5):936-959. doi: 10.1111/febs.17217

[99] Vind AC, Wu Z, Firdaus MJ, et al. The ribotoxic stress response drives acute inflammation, cell death, and epidermal thickening in UV-irradiated skin in vivo. Mol Cell. 2024; 84(24):4774-4789.e9. doi: 10.1016/j.molcel.2024.10.044

[100] Derenzini E, Agostinelli C, Rossi A, et al. Genomic alterations of ribosomal protein genes in diffuse large B cell lymphoma. Br J Haematol. 2019; 185(2):330-334. doi: 10.1111/bjh.15442

[101] Dutt S, Narla A, Lin K, et al. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood. 2011; 117(9):2567-2576. doi: 10.1182/blood-2010-07-295238

[102] Barlow JL, Drynan LF, Hewett DR, et al. A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. Nat Med. 2010; 16(1):59-66. doi: 10.1038/nm.2063

[103] Terzian T, Dumble M, Arbab F, et al. Rpl27a mutation in the sooty foot ataxia mouse phenocopies high p53 mouse models. J Pathol. 2011; 224(4):540-552. doi: 10.1002/path.2891

[104] Panić L, Tamarut S, Sticker-Jantscheff M, et al. Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation. Mol Cell Biol. 2006; 26(23):8880-8891. doi: 10.1128/MCB.00751-06

[105] Sulic S, Panic L, Barkic M, Mercep M, Uzelac M, Volarevic S. Inactivation of S 6 ribosomal protein gene in T lymphocytes activates a p53-dependent checkpoint response. Genes Dev. 2005; 19(24):3070-3082. doi: 10.1101/gad.359305

[106] Jaako P, Debnath S, Olsson K, et al. Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia. Leukemia. 2015; 29(11):2221-2229. doi: 10.1038/leu.2015.128

[107] McGowan KA, Li JZ, Park CY, et al. Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects. Nat Genet. 2008; 40(8):963-970. doi: 10.1038/ng.188

[108] Recasens-Alvarez C, Alexandre C, Kirkpatrick J, et al. Ribosomopathy-associated mutations cause proteotoxic stress that is alleviated by TOR inhibition. Nat Cell Biol. 2021; 23(2):127-135. doi: 10.1038/s41556-020-00626-1

[109] Kim TH, Leslie P, Zhang Y. Ribosomal proteins as unrevealed caretakers for cellular stress and genomic instability. Oncotarget. 2014; 5(4):860-871. doi: 10.18632/oncotarget.1784

[110] Gu J, Kawai H, Nie L, et al.Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J Biol Chem. 2002; 277(22):19251-19254. doi: 10.1074/jbc.C200150200

[111] Deisenroth C, Franklin DA, Zhang Y. The evolution of the ribosomal protein-MDM2-p53 pathway. Cold Spring Harb Perspect Med. 2016; 6(12):a026138. doi: 10.1101/cshperspect.a026138

[112] Liu Y, Deisenroth C, Zhang Y. RP-MDM2-p53 pathway: Linking ribosomal biogenesis and tumor surveillance. Trends Cancer. 2016; 2(4):191-204. doi: 10.1016/j.trecan.2016.03.002

[113] Castillo Duque de Estrada NM, Thoms M, Flemming D, et al. Structure of nascent 5S RNPs at the crossroad between ribosome assembly and MDM2-p53 pathways. Nat Struct Mol Biol. 2023; 30(8):1119-1131. doi: 10.1038/s41594-023-01006-7

[114] Sloan KE, Bohnsack MT, Watkins NJ. The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress. Cell Rep. 2013; 5(1):237-247. doi: 10.1016/j.celrep.2013.08.049

[115] Nishimura K, Kumazawa T, Kuroda T, et al. Perturbation of ribosome biogenesis drives cells into senescence through 5S RNP-mediated p53 activation. Cell Rep. 2015; 10(8):1310-1323. doi: 10.1016/j.celrep.2015.01.055

[116] Donati G, Peddigari S, Mercer CA, Thomas G. 5S ribosomal RNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint. Cell Rep. 2013; 4(1):87-98. doi: 10.1016/j.celrep.2013.05.045

[117] Dai MS, Lu H.Inhibition of MDM2-mediated p 53 ubiquitination and degradation by ribosomal protein L5. J Biol Chem. 2004; 279(43):44475-44482. doi: 10.1074/jbc.M403722200

[118] Dai MS, Zeng SX, Jin Y, Sun XX, David L, Lu H. Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition. Mol Cell Biol. 2004; 24(17):7654-7668. doi: 10.1128/mcb.24.17.7654-7668.2004

[119] Zhang Y, Wolf GW, Bhat K, et al. Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway. Mol Cell Biol. 2003; 23(23):8902-8912. doi: 10.1128/MCB.23.23.8902-8912.2003

[120] Lohrum MAE, Ludwig RL, Kubbutat MHG, Hanlon M, Vousden KH.Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell. 2003; 3(6):577-587. doi: 10.1016/s1535-6108(03)00134-x

[121] Horn HF, Vousden KH. Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway. Oncogene. 2008; 27(44):5774-5784. doi: 10.1038/onc.2008.189

[122] Bursać S, Brdovčak MC, Pfannkuchen M, et al. Mutual protectionofribosomalproteins L5 and L11 fromdegradation is essential for p53 activation upon ribosomal biogenesis stress. Proc Natl Acad Sci U S A. 2012; 109(50):20467-20472. doi: 10.1073/pnas.1218535109

[123] Zheng J, Lang Y, Zhang Q, et al. Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53 activation. Genes Dev. 2015; 29(14):1524-1534. doi: 10.1101/gad.261792.115

[124] Teng T, Mercer CA, Hexley P, Thomas G, Fumagalli S. Loss of tumor suppressor RPL5/RPL11 does not induce cell cycle arrest but impedes proliferation due to reduced ribosome content and translation capacity. Mol Cell Biol. 2013; 33(23):4660-4671. doi: 10.1128/MCB.01174-13

[125] Fumagalli S, Ivanenkov VV, Teng T, Thomas G. Suprainduction of p 53 by disruption of 40S and 60S ribosome biogenesis leads to the activation of a novel G2/M checkpoint. Genes Dev. 2012; 26(10):1028-1040. doi: 10.1101/gad.189951.112

[126] Fumagalli S, Di Cara A, Neb-Gulati A, et al. Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction. Nat Cell Biol. 2009; 11(4):501-508. doi: 10.1038/ncb1858

[127] Tagnères S, Santo PE, Radermecker J, et al. SURF2 is a MDM2 antagonist in triggering the nucleolar stress response. Nat Commun. 2024; 15(1):8404. doi: 10.1038/s41467-024-52659-x

[128] Vousden KH, Prives C.Blinded by the light: The growing complexity of p53. Cell. 2009; 137(3):413-431. doi: 10.1016/j.cell.2009.04.037

[129] Levine AJ. p53: 800 million years of evolution and 40 years of discovery. Nat Rev Cancer. 2020; 20(8):471-480. doi: 10.1038/s41568-020-0262-1

[130] Jansen J, Bohnsack KE, Böhlken-Fascher S, Bohnsack MT, Dobbelstein M.The ribosomal protein L22 binds the MDM4 pre-mRNA and promotes exon skipping to activate p53 upon nucleolar stress. Cell Rep. 2024; 43(8):114610. doi: 10.1016/j.celrep.2024.114610

[131] Chandler DS, Singh RK, Caldwell LC, Bitler JL, Lozano G. Genotoxic stress induces coordinately regulated alternative splicing of the p 53 modulators MDM2 and MDM4. Cancer Res. 2006; 66(19):9502-9508. doi: 10.1158/0008-5472.CAN-05-4271

[132] Marine JC, Jochemsen AG. MDMX (MDM4), a promising target for p53 reactivation therapy and beyond. Cold Spring Harb Perspect Med. 2016; 6(7):a026237. doi: 10.1101/cshperspect.a026237

[133] O’Leary MN, Schreiber KH, Zhang Y, et al. The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1. PLoS Genet. 2013; 9(8):e1003708. doi: 10.1371/journal.pgen.1003708

[134] Eastham MJ, Pelava A, Wells GR, et al. The induction of p53 correlates with defects in the production, but not the levels, of the small ribosomal subunit and stalled large ribosomal subunit biogenesis. Nucleic Acids Res. 2023; 51(17):9397-9414. doi: 10.1093/nar/gkad637

[135] Jansen J, Dobbelstein M. MDM4 exon skipping upon dysfunctional ribosome assembly. Trends Cell Biol. 2025; 35(7):544-547. doi: 10.1016/j.tcb.2024.10.006

[136] Zhang X, Wang W, Wang H, Wang MH, Xu W, Zhang R. Identification of ribosomal protein S25 (RPS25)-MDM2-p53 regulatory feedback loop. Oncogene. 2013; 32(22):2782-2791. doi: 10.1038/onc.2012.289

[137] Bai D, Zhang J, Xiao W, Zheng X. Regulation of the HDM2-p53 pathway by ribosomal protein L6 in response to ribosomal stress. Nucleic Acids Res. 2014; 42(3):1799-1811. doi: 10.1093/nar/gkt971

[138] Takagi M, Absalon MJ, McLure KG, Kastan MB. Regulation of p 53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell. 2005; 123(1):49-63. doi: 10.1016/j.cell.2005.07.034

[139] Ofir-Rosenfeld Y, Boggs K, Michael D, Kastan MB, Oren M. Mdm 2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell. 2008; 32(2):180-189. doi: 10.1016/j.molcel.2008.08.031

[140] Zhu Y, Poyurovsky MV, Li Y, et al. Ribosomal protein S 7 is both a regulator and a substrate of MDM2. Mol Cell. 2009; 35(3):316-326. doi: 10.1016/j.molcel.2009.07.014

[141] Vilborg A, Wilhelm MT, Wiman KG. Regulation of tumor suppressor p53 at the RNA level. J Mol Med (Berl). 2010; 88(7):645-652. doi: 10.1007/s00109-010-0609-2

[142] Kampen KR, Fancello L, Girardi T, et al. Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells. Nat Commun. 2019; 10(1):2542. doi: 10.1038/s41467-019-10508-2

[143] Kampen KR, Sulima SO, Verbelen B, et al. The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL. Leukemia. 2019; 33(2):319-332. doi: 10.1038/s41375-018-0176-z

[144] Bacci L, Indio V, Rambaldelli G, et al.Mutational analysis of ribosomal proteins in a cohort of pediatric patients with T-cell acute lymphoblastic leukemia reveals Q123R, a novel mutation in RPL10. Front Genet. 2022;13:1058468. doi: 10.3389/fgene.2022.1058468

[145] Hofman IJF, Patchett S, Van Duin M, et al. Low frequency mutations in ribosomal proteins RPL10 and RPL5 in multiple myeloma. Haematologica. 2017; 102(8):e317-e320. doi: 10.3324/haematol.2016.162198

[146] Bretones G, Álvarez MG, Arango JR, et al. Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia. Blood. 2018; 132(22):2375-2388. doi: 10.1182/blood-2017-09-804401

[147] Ntoufa S, Gerousi M, Laidou S, et al. RPS15 mutations rewire RNA translation in chronic lymphocytic leukemia. Blood Adv. 2021; 5(13):2788-2792. doi: 10.1182/bloodadvances.2020001717

[148] James A, Wang Y, Raje H, Rosby R, DiMario P.Nucleolar stress with and without p53. Nucleus. 2014; 5(5):402-426. doi: 10.4161/nucl.32235

[149] Dönig J, Mende H, Davila Gallesio J, et al. Characterization of nucleolar SUMO isopeptidases unveils a general p53- independent checkpoint of impaired ribosome biogenesis. Nat Commun. 2023; 14(1):8121. doi: 10.1038/s41467-023-43751-9

[150] Del Toro N, Fernandez-Ruiz A, Mignacca L, et al. Ribosomal protein RPL22/eL22 regulates the cell cycle by acting as an inhibitor of the CDK4-cyclin D complex. Cell Cycle. 2019; 18(6-7):759-770. doi: 10.1080/15384101.2019.1593708

[151] Lessard F, Brakier-Gingras L, Ferbeyre G. Ribosomal proteins control tumor suppressor pathways in response to nucleolar stress. Bioessays. 2019; 41(3):e1800183. doi: 10.1002/bies.201800183

[152] Dannheisig DP, Bächle J, Tasic J, Keil M, Pfister AS. The Wnt/β-catenin pathway is activated as a novel nucleolar stress response. J Mol Biol. 2021; 433(2):166719. doi: 10.1016/j.jmb.2020.11.018

[153] Donati G, Brighenti E, Vici M, et al. Selective inhibition of rRNA transcription downregulates E2F-1: A new p53-independent mechanism linking cell growth to cell proliferation. J Cell Sci. 2011; 124(Pt 17):3017-3028. doi: 10.1242/jcs.086074

[154] Lessard F, Igelmann S, Trahan C, et al. Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway. Nat Cell Biol. 2018; 20(7):789-799. doi: 10.1038/s41556-018-0127-y

[155] Dai MS, Sun XX, Lu H.Ribosomal protein L11 associates with c-Myc at 5 S rRNA and tRNA genes and regulates their expression. J Biol Chem. 2010; 285(17):12587-12594. doi: 10.1074/jbc.M109.056259

[156] Challagundla KB, Sun XX, Zhang X, et al. Ribosomal protein L11 recruits miR-24/miRISC to repress c-Myc expression in response to ribosomal stress. Mol Cell Biol. 2011; 31(19):4007-4021. doi: 10.1128/MCB.05810-11

[157] Arabi A, Wu S, Ridderstråle K, et al. c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell Biol. 2005; 7(3):303-310. doi: 10.1038/ncb1225

[158] Boon K, Caron HN, Van Asperen R, et al. N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis. EMBO J. 2001; 20(6):1383-1393. doi: 10.1093/emboj/20.6.1383

[159] Schlosser I, Hölzel M, Mürnseer M, Burtscher H, Weidle UH, Eick D. A role for c-Myc in the regulation of ribosomal RNA processing. Nucleic Acids Res. 2003; 31(21):6148-6156. doi: 10.1093/nar/gkg794

[160] Zielke N, Vähärautio A, Liu J, Kivioja T, Taipale J. Upregulation of ribosome biogenesis via canonical E-boxes is required for Myc-driven proliferation. Dev Cell. 2022; 57(8):1024-1036.e5. doi: 10.1016/j.devcel.2022.03.018

[161] Morata G, Ripoll P. Minutes: Mutants of Drosophila autonomously affecting cell division rate. Dev Biol. 1975; 42(2):211-221. doi: 10.1016/0012-1606(75)90330-9

[162] Lin JI, Mitchell NC, Kalcina M, et al. Drosophila ribosomal protein mutants control tissue growth non-autonomously via effects on the prothoracic gland and ecdysone. PLoS Genet. 2011; 7(12):e1002408. doi: 10.1371/journal.pgen.1002408

[163] Baker NE, Montagna C. Reducing the aneuploid cell burden - cell competition and the ribosome connection. Dis Model Mech. 2022; 15(11):dmm049673. doi: 10.1242/dmm.049673

[164] Watson KL, Konrad KD, Woods DF, Bryant PJ. Drosophila homolog of the human S6 ribosomal protein is required for tumor suppression in the hematopoietic system. Proc Natl Acad Sci U S A. 1992; 89(23):11302-11306. doi: 10.1073/pnas.89.23.11302

[165] Ji Z, Kiparaki M, Folgado V, et al. Drosophila RpS 12 controls translation, growth, and cell competition through Xrp1. PLoS Genet. 2019; 15(12):e1008513. doi: 10.1371/journal.pgen.1008513

[166] Baker NE, Kale A. Mutations in ribosomal proteins: Apoptosis, cell competition, and cancer. Mol Cell Oncol. 2016; 3(1):e1029065. doi: 10.1080/23723556.2015.1029065

[167] Baumgartner ME, Dinan MP, Langton PF, Kucinski I, Piddini E. Proteotoxic stress is a driver of the loser status and cell competition. Nat Cell Biol. 2021; 23(2):136-146. doi: 10.1038/s41556-020-00627-0

[168] Kiparaki M, Khan C, Folgado-Marco V, Chuen J, Moulos P, Baker NE. The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function. Elife. 2022;11:e71705. doi: 10.7554/eLife.71705

[169] Amsterdam A, Sadler KC, Lai K, et al. Many ribosomal protein genes are cancer genes in zebrafish. PLoS Biol. 2004; 2(5):E139. doi: 10.1371/journal.pbio.0020139

[170] MacInnes AW, Amsterdam A, Whittaker CA, Hopkins N, Lees JA. Loss of p 53 synthesis in zebrafish tumors with ribosomal protein gene mutations. Proc Natl Acad Sci U S A. 2008; 105(30):10408-10413. doi: 10.1073/pnas.0805036105

[171] Lai K, Amsterdam A, Farrington S, Bronson RT, Hopkins N, Lees JA. Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish. Dev Dyn. 2009; 238(1):76-85. doi: 10.1002/dvdy.21815

[172] Vishwakarma M, Piddini E. Outcompeting cancer. Nat Rev Cancer. 2020; 20(3):187-198. doi: 10.1038/s41568-019-0231-8

[173] Lorenzo-Martín LF, Robles-Valero J, Ramírez-Cota R, et al. Ribosomal protein deficiencies linked to Diamond-Blackfan anemia induce distinctive alterations of ATF4 expression. iScience. 2025; 28(4):112138. doi: 10.1016/j.isci.2025.112138

[174] Hannan KM, Sanij E, Hein N, Hannan RD, Pearson RB.Signaling to the ribosome in cancer--it is more than just mTORC1. IUBMB Life. 2011; 63(2):79-85. doi: 10.1002/iub.428

[175] Albert B, Kos-Braun IC, Henras AK, et al. A ribosome assembly stress response regulates transcription to maintain proteome homeostasis. Elife. 2019;8:e45002. doi: 10.7554/eLife.45002

[176] Comerford SA, Hinnant EA, Chen Y, Hammer RE. Hepatic ribosomal protein S6 (Rps6) insufficiency results in failed bile duct development and loss of hepatocyte viability; a ribosomopathy-like phenotype that is partially p53- dependent. PLoS Genet. 2023; 19(1):e1010595. doi: 10.1371/journal.pgen.1010595

[177] Machado HE, Øbro NF, Williams N, et al. Convergent somatic evolution commences in utero in a germline ribosomopathy. Nat Commun. 2023; 14(1):5092. doi: 10.1038/s41467-023-40896-5

[178] Morgado-Palacin L, Varetti G, Llanos S, Gómez-López G, Martinez D, Serrano M. Partial loss of Rpl11 in adult mice recapitulates diamond-blackfan anemia and promotes lymphomagenesis. Cell Rep. 2015; 13(4):712-722. doi: 10.1016/j.celrep.2015.09.038

[179] Rao S, Cai KQ, Stadanlick JE, et al. Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma. Cancer Res. 2016; 76(11):3387-3396. doi: 10.1158/0008-5472.can-15-2698

[180] Kazerounian S, Ciarlini PD, Yuan D, et al. Development of soft tissue sarcomas in ribosomal proteins L5 and S24 heterozygous mice. J Cancer. 2016; 7(1):32-36. doi: 10.7150/jca.13292

[181] Barna M, Pusic A, Zollo O, et al. Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency. Nature. 2008; 456(7224):971-975. doi: 10.1038/nature07449

[182] Warner JR. In the absence of ribosomal RNA synthesis, the ribosomal proteins of HeLa cells are synthesized normally and degraded rapidly. J Mol Biol. 1977; 115(3):315-333. doi: 10.1016/0022-2836(77)90157-7

[183] Ohashi A, Ohori M, Iwai K, et al. Aneuploidy generates proteotoxic stress and DNA damage concurrently with p53- mediated post-mitotic apoptosis in SAC-impaired cells. Nat Commun. 2015;6:7668. doi: 10.1038/ncomms8668

[184] Tye BW, Commins N, Ryazanova LV, et al. Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness. Elife. 2019;8:e43002. doi: 10.7554/eLife.43002

[185] Malik Ghulam M, Catala M, Reulet G, Scott MS, Abou Elela S. Duplicated ribosomal protein paralogs promote alternative translation and drug resistance. Nat Commun. 2022; 13(1):4938. doi: 10.1038/s41467-022-32717-y

[186] Rao S, Peri S, Hoffmann J, et al. RPL22L1 induction in colorectal cancer is associated with poor prognosis and 5-FU resistance. PLoS One. 2019; 14(10):e0222392. doi: 10.1371/journal.pone.0222392

[187] McDonald ER, De Weck A, Schlabach MR, et al. Project DRIVE: A compendium of cancer dependencies and synthetic lethal relationships uncovered by large-scale, deep RNAi screening. Cell. 2017; 170(3):577-592.e10. doi: 10.1016/j.cell.2017.07.005

[188] Sugihara Y, Honda H, Iida T, et al. Proteomic analysis of rodent ribosomes revealed heterogeneity including ribosomal proteins L10-like, L22-like 1, and L39-like. J Proteome Res. 2010; 9(3):1351-1366. doi: 10.1021/pr9008964

[189] Zou Q, Qi H. Deletion of ribosomal paralogs Rpl39 and Rpl39l compromises cell proliferation via protein synthesis and mitochondrial activity. Int J Biochem Cell Biol. 2021;139:106070. doi: 10.1016/j.biocel.2021.106070

[190] Tian Y, Chen L, Jiang Y. LASSO-based screening for potential prognostic biomarkers associated with glioblastoma. Front Oncol. 2022;12:1057383. doi: 10.3389/fonc.2022.1057383

[191] Fisher EM, Beer-Romero P, Brown LG, et al. Homologous ribosomal protein genes on the human X and Y chromosomes: Escape from X inactivation and possible implications for Turner syndrome. Cell. 1990; 63(6):1205-1218. doi: 10.1016/0092-8674(90)90416-c

[192] Sun XX, Dai MS, Lu H. 5-fluorouracil activation of p53 involves an MDM2-ribosomal protein interaction. J Biol Chem. 2007; 282(11):8052-8059. doi: 10.1074/jbc.M610621200

[193] Sun XX, Dai MS, Lu H. Mycophenolic acid activation of p 53 requires ribosomal proteins L5 and L11. J Biol Chem. 2008; 283(18):12387-12392. doi: 10.1074/jbc.M801387200

[194] Bhat KP, Itahana K, Jin A, Zhang Y.Essential role of ribosomal protein L11 in mediating growth inhibition- induced p53 activation. EMBO J. 2004; 23(12):2402-2412. doi: 10.1038/sj.emboj.7600247

[195] Hannan KM, Soo P, Wong MS, et al. Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway. Cell Rep. 2022; 41(5):111571. doi: 10.1016/j.celrep.2022.111571

[196] Kawahata T, Kawahara K, Shimokawa M, et al. Involvement of ribosomal protein L11 expression in sensitivity of gastric cancer against 5-FU. Oncol Lett. 2020; 19(3):2258-2264. doi: 10.3892/ol.2020.11352

[197] Han T, Tong J, Wang M, et al. Olaparib induces RPL5/ RPL11-dependent p53 activation via nucleolar stress. Front Oncol. 2022;12:821366. doi: 10.3389/fonc.2022.821366

[198] Ishihara Y, Nakamura K, Nakagawa S, et al. Nucleolar stress response via ribosomal protein l11 regulates topoisomerase inhibitor sensitivity of P53-intact cancers. Int J Mol Sci. 2022; 23(24):15986. doi: 10.3390/ijms232415986

[199] Howard GC, Wang J, Rose KL, et al. Ribosome subunit attrition and activation of the p53-MDM4 axis dominate the response of MLL-rearranged cancer cells to WDR5 WIN site inhibition. Elife. 2024;12:RP90683. doi: 10.7554/eLife.90683

[200] McIntosh KB, Bhattacharya A, Willis IM, Warner JR. Eukaryotic cells producing ribosomes deficient in Rpl1 are hypersensitive to defects in the ubiquitin-proteasome system. PLoS One. 2011; 6(8):e23579. doi: 10.1371/journal.pone.0023579

[201] Gilles A, Frechin L, Natchiar K, et al. Targeting the human 80S ribosome in cancer: From structure to function and drug design for innovative adjuvant therapeutic strategies. Cells. 2020; 9(3):629. doi: 10.3390/cells9030629

[202] Hofman IJF, Van Duin M, De Bruyne E, et al. RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response. Leukemia. 2017; 31(8):1706-1714. doi: 10.1038/leu.2016.370

[203] Robak P, Jarych D, Mikulski D, et al. The prognostic value of whole-blood PSMB5, CXCR4, POMP, and RPL5 mRNA expression in patients with multiple myeloma treated with bortezomib. Cancers (Basel). 2021; 13(5):951. doi: 10.3390/cancers13050951

[204] Ren Y, Tao C, Wang X, Ju Y. Identification of RPL5 and RPL10 as novel diagnostic biomarkers of Atypical teratoid/rhabdoid tumors. Cancer Cell Int. 2018;18:190. doi: 10.1186/s12935-018-0681-1

[205] D’Andrea G, Deroma G, Miluzio A, Biffo S. The paradox of ribosomal insufficiency coupled with increased cancer: Shifting the perspective from the cancer cell to the microenvironment. Cancers (Basel). 2024; 16(13):2392. doi: 10.3390/cancers16132392