Cell cycle regulation of the BRCA1/acetyl-CoA-carboxylase complex.
Germ-line alterations in BRCA1 are associated with an increased susceptibility to breast and ovarian cancer. The BRCA1 protein has been implicated in multiple cellular functions. We have recently demonstrated that BRCA1 reduces acetyl-CoA-carboxylase alpha (ACCA) activity through its phospho-dependent binding to ACCA, and further established that the phosphorylation of the Ser1263 of ACCA is required for this interaction. Here, to gain more insight into the cellular conditions that trigger the BRCA1/ACCA interaction, we designed an anti-pSer1263 antibody and demonstrated that the Ser1263 of ACCA is phosphorylated in vivo, in a cell cycle-dependent manner. We further showed that the interaction between BRCA1 and ACCA is regulated during cell cycle progression. Taken together, our findings reveal a novel mechanism of regulation of ACCA distinct from the previously described phosphorylation of Ser79, and provide new insights into the control of lipogenesis through the cell cycle.
Ray
H
H
CNRS UMR5201, Laboratoire Génétique Moléculaire Signalisation et Cancer, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France.
Suau
F
F
Vincent
A
A
Dalla Venezia
N
N
D000103:Acetyl-CoA Carboxylase / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology; D045163:Antibodies, Phospho-Specific / Q000276:immunology; D019313:BRCA1 Protein / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D006801:Humans; D050155:Lipogenesis; D010766:Phosphorylation; D010768:Phosphoserine / Q000276:immunology; D025941:Protein Interaction Mapping; D012694:Serine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D045163:Antibodies, Phospho-Specific; D019313:BRCA1 Protein; D010768:Phosphoserine; D012694:Serine; D018844:Cyclin-Dependent Kinases; D000103:Acetyl-CoA Carboxylase