title: The C-terminal proteolytic fragment of the breast cancer susceptibility type 1 protein (BRCA1) is degraded by the N-end rule pathway.
abstract: The breast cancer susceptibility type 1 gene product (BRCA1) is cleaved by caspases upon the activation of apoptotic pathways. After proteolysis the C-terminal fragment has been reported to translocate to the cytoplasm and promote cell death. Here we report that the C-terminal fragment is unstable in cells as it is targeted for degradation by the N-end rule pathway. The data reveals that mutating the wild type N-terminal aspartate, of the C-terminal fragment, to valine stabilizes the fragment. If the N terminus is mutated to another N-terminal destabilizing residue, like arginine, the C-terminal fragment remains unstable in cells. Last, the C-terminal fragment of BRCA1 is stable in cells lacking ATE1, a component of the N-end rule pathway.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Xu
authors.forename: Roshani
authors.initials: R
authors.lastname: Payoe
authors.forename: Richard P
authors.initials: RP
authors.lastname: Fahlman
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D020169:Caspases