Inhibition of G1 to S cell cycle progression by BCCIP beta

The BCCIP alpha 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 BCCIP alpha enhances the inhibitory activity of p21 toward CDK2 and that BCCIP alpha inhibits the growth of certain tumor cells. Here we show that a second isoform, BCCIP beta, also binds to p21 and inhibits cell growth. The growth inhibition by BCCIP beta can be partially abrogated in p21 deficient cells. Overexpression of BCCIP beta delays the G1 to S progression and results in an elevated p21 expression. These data suggest BCCIP beta as a new regulator for the G1-S cell cycle progression and cell growth control.