Characterization of the Interactions of BRCA1 and Protein Phosphatase 1
Abstract
The breast cancer susceptibility gene BRCAl is mutated in many cases of familial breast and ovarian cancer. BRCAl is phosphorylated from S to M phase of the cell cycle, as well as in response to DNA damage, and a hypophosphorylated form of BRCAl is found at the centrosome during M phase of the cell cycle. Phosphorylation may play an important role in the regulation of BRCAl function. We have performed a yeast two-hybrid study in order to identify proteins that interact with exonll of BRCAl. Among the proteins identified in the screen was Protein Phosphatase 1 (PPl), a serine threonine phosphatase. PPl and BRCAl co-immunoprecipitate both in vitro and in vivo, and a GST pull down assay has identified the region within BRCAl that is involved in the interaction. Colocalization studies of the two proteins provide further evidence for an interaction of BRCAl and PPl within the nucleus of the cell. Mutational analysis has identified 2 sequence alterations in PPl alpha, and expression analysis of PPl mRNA has been performed. Studies also show that PPl alpha dephosphorylates BRCAl in vitro. The interaction of PPl and BRCAl represents a potentially significant interaction that could have an affect on the function of BRCAl.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425725
Entities
People
- Sherry L. Hendry
Organizations
- Mount Sinai Hospital, Toronto