SEI family of nuclear factors regulates p53‐dependent transcriptional activation

SEI family proteins, p34SEI‐1 and SEI‐2(TRIP‐Br2), are nuclear factors that are implicated in cell cycle regulation through interaction with CDK4/CyclinD and E2F‐1/DP‐1 complexes. Here we report that the SEI family proteins regulate transcriptional activity of p53 tumor suppressor protein. Expression of SEI‐1, SEI‐2 or SEI‐3 strongly stimulates p53‐dependent gene activation in HeLa and U2OS cells but not in p53‐deficient Saos2 or p53‐knockdown HeLa cells. SEI proteins possess an intrinsic transactivation activity, interact with the coactivator CREB‐binding protein, and cooperate synergistically with the ING family of chromatin‐associated proteins to stimulate the transactivation function of p53. Doxycycline‐induced expression of SEI proteins results in activation of the p21 gene and inhibition of cell growth, but the growth arrest was not suppressed by the siRNA‐mediated knockdown of the endogenous p53 protein. These results indicate that the SEI family of nuclear proteins regulates p53 transcriptional activity and a p53‐independent signaling pathway leading to growth inhibition.