이혜민 (Tulane University School of Medicine)

한빛사논문

조회215

Tulane University School of Medicine

Proc. Natl. Acad. Sci. USA, Dec 05 2023, 120 (49) | https://doi.org/10.1073/pnas.2308292120 RNA-binding motif protein 10 inactivates c-Myc by partnering with ribosomal proteins uL18 and uL5

Hyemin Lee ^{1 2}, Ji Hoon Jung ^{1 2}, Hyun Min Ko ^{1 2}, Heewon Park^{1 2}, Allyson M Segall ^{1 2 3}, Roger L Sheffmaker ^{1 2 4}, Jieqiong Wang ^{1 2,} Wesley D Frey^{1 2}, Nathan Pham ^{1 2}, Yongbo Wang ⁵, Yiwei Zhang ^{1 2}, James G Jackson ^{1 2}, Shelya X Zeng ^{1 2}, Hua Lu ^{1 2 *}

¹Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.
²Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112.
³Department of Neuroscience, Tulane University, New Orleans, LA 70118.
⁴Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118.
⁵Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

^*Corresponding author: correspondence to Hua Lu

Abstract

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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-04)
연구진국외 연구진
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