RNA-binding motif protein 10 inactivates c-Myc by partnering with ribosomal proteins uL18 and uL5.

Autor:	Lee H; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Jung JH; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Ko HM; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Park H; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Segall AM; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112.; Department of Neuroscience, Tulane University, New Orleans, LA 70118., Sheffmaker RL; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112.; Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118., Wang J; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Frey WD; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Pham N; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Wang Y; Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Zhang Y; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Jackson JG; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Zeng SX; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112., Lu H; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Dec 05; Vol. 120 (49), pp. e2308292120. Date of Electronic Publication: 2023 Nov 30.
DOI:	10.1073/pnas.2308292120
Abstrakt:	RNA-binding motif protein 10 (RBM10) is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). Yet, it remains unknown whether cancer-derived mutant RBM10 compromises its tumor suppression function and, if so, the molecular insight of the underlying mechanisms. Here, we show that wild-type RBM10 suppresses lung cancer cell growth and proliferation by inactivating c-Myc that is essential for cancer cell survival. RBM10 directly binds to c-Myc and promotes c-Myc's ubiquitin-dependent degradation, while RBM10 knockdown leads to the induction of c-Myc level and activity. This negative action on c-Myc is further boosted by ribosomal proteins (RPs) uL18 (RPL5) and uL5 (RPL11) via their direct binding to RBM10. Cancer-derived mutant RBM10-I316F fails to bind to uL18 and uL5 and to inactivate c-Myc, thus incapable of suppressing tumorigenesis. Our findings uncover RBM10 as a pivotal c-Myc repressor by cooperating with uL18 and uL5 in lung cancer cells, as its failure to do so upon mutation favors tumorigenesis. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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