Inhibition of G1 to S Cell Cycle Progression by BCCIPß

The BCCIPalpha protein was identified as a BRCA2 and CDKN1A (p21, or p21(Waf1/Cip1)) Interacting Protein. It binds to a highly conserved domain proximate to the C-terminus of BRCA2 protein and the C-terminal domain of the CDK-inhibitor p21. Previous reports showed that BCCIPa enhances the inhibitory activity of p21 toward CDK2 and that BCCIPalpha inhibits the growth of certain tumor cells. Here we show that a second isoform, BCCIbeta, also binds to p21 and inhibits cell growth. The growth inhibition by BCCIPbeta can be partially abrogated in p21 deficient cells. Overexpression of BCCIPbeta delays the G1 to S progression and results in an elevated p21 expression. These data suggest BCCIPbeta as a new regulator for the G(1)-S cell cycle progression and cell growth control.