title: The MYC-associated protein CDCA7 is phosphorylated by AKT to regulate MYC-dependent apoptosis and transformation.
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.
authors.affiliation: Department of Biology, York University, Toronto, Ontario, Canada.
authors.forename: R Montgomery
authors.initials: RM
authors.lastname: Gill
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Gabor
authors.forename: Amber L
authors.initials: AL
authors.lastname: Couzens
authors.forename: Michael P
authors.initials: MP
authors.lastname: Scheid
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment
chemical_list: D048948:14-3-3 Proteins; C445325:CDCA7 protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D051057:Proto-Oncogene Proteins c-akt