title: Characterization of a carboxy-terminal BRCA1 interacting protein.
abstract: There are several lines of evidence indicating that the carboxy-terminal region of the tumor suppressor protein BRCA1 is a functionally significant domain. Using the yeast two-hybrid and in vitro biochemical assays, we show that a protein, CtIP, interacts specifically with the carboxy-terminal segment of human BRCA1 from residues 1602-1863. A germ line truncation mutation, Y1853ter, that removes the last 11 amino acids from the carboxy-terminus of BRCA1, abolishes not only its transcriptional activation function, but also binding to CtIP. The function of CtIP is unknown, but its reported association with a transcriptional repressor CtBP lends further support that it may have a role in transcription. A sequence based screen of a panel of 89 tumor cell line cDNAs for mutations in the CtIP coding region identified five missense variants. In the pancreatic carcinoma cell line, BxPC3, the non-conservative lysine to glutamic acid change at codon 337 is accompanied with apparent loss of heterozygosity or non-expression of the wild type allele. Thus it is plausible that CtIP may itself be a tumor suppressor acting in the same pathway as BRCA1.
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, Utah 84108, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Wong
authors.forename: P A
authors.initials: PA
authors.lastname: Ormonde
authors.forename: R
authors.initials: R
authors.lastname: Pero
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Lian
authors.forename: G
authors.initials: G
authors.lastname: Salada
authors.forename: S
authors.initials: S
authors.lastname: Berry
authors.forename: Q
authors.initials: Q
authors.lastname: Lawrence
authors.forename: P
authors.initials: P
authors.lastname: Dayananth
authors.forename: P
authors.initials: P
authors.lastname: Ha
authors.forename: S V
authors.initials: SV
authors.lastname: Tavtigian
authors.forename: D H
authors.initials: DH
authors.lastname: Teng
authors.forename: P L
authors.initials: PL
authors.lastname: Bartel
mesh_terms: D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D017930:Genes, Reporter; D018095:Germ-Line Mutation; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D001616:beta-Galactosidase