The RhoGAP domain-containing protein, Porf-2, inhibits proliferation and enhances apoptosis in neural stem cells

Neural stem cells (NSCs) are essential to developing and mature CNS. They shape the structural and functional layouts of the brain in developing CNS and continue to proliferate, generating new neurons in several adult brain regions. Preoptic regulatory factor-2 (Porf-2), a RhoGAP domain-containing protein expressed in CNS, has a role in gender-related brain development and function. Porf-2 expression was knocked down in C17.2, a mouse cerebellar multipotent cell line. This increased proliferation and decreased drug-induced apoptosis without affecting cell type distribution following differentiation induction. It lowered levels of cyclin kinase inhibitor p21, affected G1 to S phase cell cycle transition; partially blocked the elevation in p53 transcriptional activity, p21 and Bcl-2-associated X protein (Bax) levels caused by bleomycin, but had no influence on enhancement of Bax in response to staurosporine. Thus Porf-2 may inhibit NSC proliferation by enhancing p21 protein levels followed by G1 phase arrest; it plays pro-apoptotic roles in response to drug treatment through both p53 transcription-dependent and independent pathways. This is consistent with categorization of Porf-2 as a functional RhoGAP in CNS.