过表达UHRF2通过上调p53及p21表达引起HEK293细胞G1期阻滞

UHRF2（ubiquitin like with PHD and ring finger domains 2）是新近发现的具有多个结构域的核蛋白，在细胞周期调控和表观遗传学中发挥重要作用．近期研究提示，UHRF2是肿瘤抑制蛋白p53的1个E3连接酶，在体内外能与p53相互结合并促进其泛素化，过表达UHRF2能使细胞周期停滞于G1期．然而，UHRF2介导的G1期阻滞及其与p53联系尚不清楚．通过共转染UHRF2质粒及p53特异性小干扰RNA(siRNAs)到HEK293细胞构建细胞模型，探索UHRF2引起细胞周期停滞与p53之间的关系．结果显示，UHRF2能促进HEK293细胞中p53的稳定，从而引起p21 (CIP1/WAF1)基因表达，并使细胞周期停滞于G1期；但在siRNA抑制p53的表达后p21(CIP1/WAF1)表达降低，UHRF2引起的细胞周期阻滞消除．研究结果提示，UHRF2可通过稳定p53，上调p21的表达，从而介导细胞周期阻滞于G1期；同时UHRF2可能参与细胞周期调控及DNA损伤反应（DNA damage response, DDR）．UHRF2稳定p53的具体分子机制及其在DDR中的作用有待进一步研究证明．

Overexpression of UHRF2 Induces HEK293 Cell Arrest at G1 Phase through Upregulating p53 and p21(CIP1/WAF1)

UHRF2（ubiquitin like with PHD and ring finger domains 2）is a multi domain nuclear protein that plays an important role in the regulation of cell cycle and in epigenetic modifications. UHRF2 has been shown to be a novel E3 ubiquitin ligase mediating the ubiquitination of tumor suppressor p53 in vivo and in vitro. In addition, overexpression of UHRF2 induces cell arrest at G1 phase. However, the linking between UHRF2 and p53, and its role in the regulation of cell cycle are not fully understood. Herein, we report a new role of UHRF2 in the regulation of p53 expression, which may induce HEK293 cell arrest at the G1 phase through upregulating p53-dependent p21(CIP1/WAF1) expression. Western blotting showed that overexpression of UHRF2 increased p53 as well as p21 expression in UHRF2 transfected HEK293 cells, but transfection of ΔRING-UHRF2 could not do so, indicating that UHRF2 may stabilize p53 protein. Furthermore, the combination of transfection with flow cytometric analyses revealed that overexpression of UHRF2 increased G1 population in HEK293 cells. However, knock-down of p53 by RNA interference (RNAi) abrogated UHRF2 overexpression induced G1 arrest, indicating that UHRF2-induced G1 arrest is attributed to increased p53 and p53-dependent p21 expression. These results suggest that overexpression of UHRF2 may induce G1 arrest through upregulating p53 dependent p21 expression, which is presumably involved in the regulation of cell cycle and DNA damage response (DDR). The mechanisms by that UHRF2 stabilizes p53 and its role in DDR need to be done in the future.