The MYC-associated Protein CDCA7 is Phosphorylated by AKT to Regulate MYC-dependent Apoptosis and Transformation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2012 Nov 21

PMID 23166294

Citations 39

Authors

R Montgomery Gill

Timothy V Gabor

Amber L Couzens

Michael P Scheid

Affiliations

Soon will be listed here.

Abstract

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 Δ(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.

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