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

Nature communications (2019-01-19)
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
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 HRasG12V 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.

MATERIALS
Product Number
Brand
Product Description

Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Ras Antibody, clone RAS10, clone RAS10, Upstate®, from mouse