Characterization of a Carboxy-Terminal BRCA1 Interacting Protein

Oncogene. 1998 Nov 5;17(18):2279-85. doi: 10.1038/sj.onc.1202150.

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.

MeSH terms

  • Amino Acid Sequence
  • BRCA1 Protein / chemistry*
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • Base Sequence
  • Genes, Reporter
  • Germ-Line Mutation
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • BRCA1 Protein
  • Peptide Fragments
  • RNA, Messenger
  • beta-Galactosidase

Associated data

  • GENBANK/U72066