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Cullin 3 targets methionine adenosyltransferase IIα for ubiquitylation‐mediated degradation and regulates colorectal cancer cell proliferation
Author(s) -
Wang Jian,
Zhu ZiHua,
Yang HongBin,
Zhang Ye,
Zhao XiangNing,
Zhang Min,
Liu YingBin,
Xu YingYing,
Lei QunYing
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13759
Subject(s) - cullin , methionine adenosyltransferase , colorectal cancer , ubiquitin , cancer research , degradation (telecommunications) , cell growth , chemistry , microbiology and biotechnology , cancer , methionine , ubiquitin ligase , biochemistry , biology , computer science , genetics , amino acid , gene , telecommunications
Cullin 3 (CUL3) serves as a scaffold protein and assembles a large number of ubiquitin ligase complexes. It is involved in multiple cellular processes and plays a potential role in tumor development and progression. In this study, we demonstrate that CUL3 targets methionine adenosyltransferase IIα (MAT IIα) and promotes its proteasomal degradation through the ubiquitylation‐mediated pathway. MAT IIα is a key enzyme in methionine metabolism and is associated with uncontrolled cell proliferation in cancer. We presently found that CUL3 down‐regulation could rescue folate deprivation‐induced MAT IIα exhaustion and growth arrest in colorectal cancer (CRC) cells. Further results from human CRC samples display an inverse correlation between CUL3 and MAT IIα protein levels. Our observations reveal a novel role of CUL3 in regulating cell proliferation by controlling the stability of MAT IIα.