Association of C-Terminal Ubiquitin Hydrolase BRCA1-Associated Protein 1 with Cell Cycle Regulator Host Cell Factor 1

• DOI: 10.1128/mcb.01517-08
• Publication Date: 2009-02-03T01:58:53Z
• Authors: Shahram Misaghi; Søren Ottosen; Anita Izrael-Toma...; David Arnott; Mohamed Lamkanfi; James Lee; Jinfeng Liu; Karen O'Rourke; Vishva M. Dixit; Angus C. Wilson
• Keywords: Deubiquitinating enzyme

Protein ubiquitination provides an efficient and reversible mechanism to regulate cell cycle progression checkpoint control. Numerous regulatory proteins direct the addition of ubiquitin lysine residues on target proteins, these are countered by army deubiquitinating enzymes (DUBs). BRCA1-associated protein-1 (Bap1) is a carboxy-terminal hydrolase frequently mutated in lung sporadic breast tumors. Bap1 can suppress growth cancer cells athymic nude mice this requires its DUB activity. We show here that interacts with host factor 1 (HCF-1), transcriptional cofactor found number important complexes. binds HCF-1 β-propeller using variant HCF-binding motif herpes simplex virus VP16 other HCF-interacting proteins. K48 K63 ubiquitinated, major site linkage at lysines 1807 1808 HCF-1C subunit. Expression catalytically inactive version results selective accumulation ubiquitinated polypeptides. Depletion small interfering RNA modest HCF-1C, suggesting helps control proliferation regulating protein levels associating genes involved G1-S transition.