Carboxy-terminal BRCA1 interacting protein

Details Carboxy-terminal BRCA1 interacting protein Carboxy-terminal BRCA1 interacting protein

1997-11-21

2000-02-29

Park, Hankyel

Chemistry: molecular biology and microbiology

Vector, per se

536 231, 4352523, 435 693, C12N 1500, C12N 120, C07H 2102, C12P 2106

Patent

active

06030832&

ABSTRACT:
Recent evidence indicates that the carboxy-terminal region of the tumor suppressor protein BRCA1 is a functionally significant domain. Using the yeast two-hybrid assay and an in vitro biochemical assay, it is here shown that a protein, B112, interacts specifically with the carboxy-terminal segment of human BRCA1 from residue 1602 to 1863. A germ line truncation mutation, 1853ter, that removes the last 11 amino acids from the carboxy-terminus of BRCA1 abolishes not only the transcription activation function, but also binding to B112. The B112 protein is apparently the same as an uncharacterized protein known as CtIP, the sequence of which was previously deposited in GenBank. Screenings of a panel of 92 tumor cell lines for mutations in the B112/CtIP sequence have identified a number of missense variants, including a non-conserved lysine to glutamic acid change at codon 337 in the pancreatic cancer line, BxPC3. Taken together, these results indicate that B112/CtIP participates in a common biochemical pathway as BRCA1 and that the interaction of these two proteins may be required for the tumor suppressor function of BRCA1.

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