First Author | Gill RM | Year | 2013 |
Journal | Mol Cell Biol | Volume | 33 |
Issue | 3 | Pages | 498-513 |
PubMed ID | 23166294 | Mgi Jnum | J:194226 |
Mgi Id | MGI:5471217 | Doi | 10.1128/MCB.00276-12 |
Citation | Gill RM, et al. (2013) The MYC-associated protein CDCA7 is phosphorylated by AKT to regulate MYC-dependent apoptosis and transformation. Mol Cell Biol 33(3):498-513 |
abstractText | 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. |