Department of Biological Sciences, Ohio University, Athens, OH 45701, USA.
Mol Cell Neurosci. 2011 Mar;46(3):573-82. doi: 10.1016/j.mcn.2010.12.008. Epub 2010 Dec 24.
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.
神经干细胞（NSCs）对于中枢神经系统的发育和成熟至关重要。它们在发育中的中枢神经系统中塑造了大脑的结构和功能布局，并继续增殖，在几个成年大脑区域产生新的神经元。前脑调节因子-2（Porf-2）是一种在中枢神经系统中表达的含有RhoGAP 结构域的蛋白质，在性别相关的大脑发育和功能中发挥作用。在 C17.2 中敲低了 Porf-2 的表达，C17.2 是一种小鼠小脑多能细胞系。这增加了增殖，减少了药物诱导的细胞凋亡，而不影响分化诱导后的细胞类型分布。它降低了细胞周期蛋白激酶抑制剂 p21 的水平，影响了 G1 到 S 期细胞周期的转变；部分阻断了博莱霉素引起的 p53 转录活性、p21 和 Bcl-2 相关 X 蛋白（Bax）水平的升高，但对 staurosporine 引起的 Bax 增强没有影响。因此，Porf-2 可能通过增强 p21 蛋白水平来抑制 NSC 的增殖，从而导致 G1 期停滞；它通过 p53 转录依赖性和非依赖性途径对药物治疗发挥促凋亡作用。这与 Porf-2 在中枢神经系统中被归类为功能性 RhoGAP 一致。
