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Targeted polyubiquitylation of RASSF1C by the Mule and SCFbeta-TrCP ligases in response to DNA damage.

Biochem J.. 2012-01;  441(1):227-36
Xin Zhou, Ting?Ting Li, Xu Feng, Esther Hsiang, Yue Xiong, Kun?Liang Guan and Qun?Ying Lei. Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China; School of Life Sciences, Fudan University, Shanghai 200032, China
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摘要

RASSF1A [Ras association (RalGDS/AF-6) domain family member 1A] and RASSF1C are two ubiquitously expressed isoforms of the RASSF1 gene. The promoter of RASSF1A is frequently hypermethylated, resulting in inactivation in various human cancers. RASSF1A is implicated in the regulation of apoptosis, microtubule stability and cell cycle arrest. However, little is known about the regulation and function of RASSF1C. In the present study we show that exogenously expressed RASSF1C is a very unstable protein that is highly polyubiquitylated and degraded via the proteasome. Furthermore, RASSF1C degradation is enhanced when cells are exposed to stress signals, such as UV irradiation. Mule, a HECT (homologous with E6-associ... More

关键词

DNA damage; glycogen synthase kinase 3 (GSK3); phosphoinositide 3-kinase (PI3K); stability; Ras association (RalGDS/AF-6) domain family member 1C (RASSF1C); ubiquitylation.