The MYC-Associated Protein CDCA7 Is Phosphorylated by AKT To Regulate MYC-Dependent Apoptosis and Transformation

被引：61

作者：

Gill, R. Montgomery ^{[1
]}

Gabor, Timothy V. ^{[1
]}

Couzens, Amber L. ^{[1
]}

Scheid, Michael P. ^{[1
]}

机构：

[1] York Univ, Dept Biol, Toronto, ON M3J 2R7, Canada

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2013年 / 33卷 / 03期

关键词：

CELL-CYCLE PROGRESSION; C-MYC; TRANSCRIPTION FACTOR; KINASE AKT; IN-VIVO; SURVIVAL; EXPRESSION; GENE; P53; PROLIFERATION;

D O I：

10.1128/MCB.00276-12

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cell division control protein A7 (CDCA7) is a recently identified target of MYC-dependent transcriptional regulation. We have discovered that CDCA7 associates with MYC and that this association is modulated in a phosphorylation-dependent manner. The prosurvival kinase AKT phosphorylates CDCA7 at threonine 163, promoting binding to 14-3-3, dissociation from MYC, and sequestration to the cytoplasm. Upon serum withdrawal, induction of CDCA7 expression in the presence of MYC sensitized cells to apoptosis, whereas CDCA7 knockdown reduced MYC-dependent apoptosis. The transformation of fibroblasts by MYC was reduced by coexpression of CDCA7, while the non-MYC-interacting protein Delta(156-187)-CDCA7 largely inhibited MYC-induced transformation. These studies provide insight into a new mechanism by which AKT signaling to CDCA7 could alter MYC-dependent growth and transformation, contributing to tumorigenesis.

引用

页码：498 / 513

页数：16

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