WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation

Woo Jeong Jeong, Jong Chan Park, Woo Shin Kim, Eun Ji Ro, Soung Hoo Jeon, Sang Kyu Lee, Young Nyun Park, Do Sik Min, Kang-Yell Choi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Stability regulation of RAS that can affect its activity, in addition to the oncogenic mutations, occurs in human cancer. However, the mechanisms for stability regulation of RAS involved in their activity and its roles in tumorigenesis are poorly explored. Here, we identify WD40-repeat protein 76 (WDR76) as one of the HRAS binding proteins using proteomic analyses of hepatocellular carcinomas (HCC) tissue. WDR76 plays a role as an E3 linker protein and mediates the polyubiquitination-dependent degradation of RAS. WDR76-mediated RAS destabilization results in the inhibition of proliferation, transformation, and invasion of liver cancer cells. WDR76 −/− mice are more susceptible to diethylnitrosamine-induced liver carcinogenesis. Liver-specific WDR76 induction destabilizes Ras and markedly reduces tumorigenesis in HRas G12V mouse livers. The clinical relevance of RAS regulation by WDR76 is indicated by the inverse correlation of their expressions in HCC tissues. Our study demonstrates that WDR76 functions as a tumor suppressor via RAS degradation.

Original languageEnglish
Article number295
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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suppressors
Tumors
Carrier Proteins
tumors
degradation
proteins
Degradation
Liver
liver
Neoplasms
Proteins
Carcinogenesis
cancer
Hepatocellular Carcinoma
mice
Diethylnitrosamine
Tissue
Liver Neoplasms
WD40 Repeats
Proteomics

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Jeong, Woo Jeong ; Park, Jong Chan ; Kim, Woo Shin ; Ro, Eun Ji ; Jeon, Soung Hoo ; Lee, Sang Kyu ; Park, Young Nyun ; Min, Do Sik ; Choi, Kang-Yell. / WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation. In: Nature communications. 2019 ; Vol. 10, No. 1.
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Jeong, WJ, Park, JC, Kim, WS, Ro, EJ, Jeon, SH, Lee, SK, Park, YN, Min, DS & Choi, K-Y 2019, 'WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation', Nature communications, vol. 10, no. 1, 295. https://doi.org/10.1038/s41467-018-08230-6

WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation. / Jeong, Woo Jeong; Park, Jong Chan; Kim, Woo Shin; Ro, Eun Ji; Jeon, Soung Hoo; Lee, Sang Kyu; Park, Young Nyun; Min, Do Sik; Choi, Kang-Yell.

In: Nature communications, Vol. 10, No. 1, 295, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Choi, Kang-Yell

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