Effects of MdmX on Mdm2‐mediated downregulation of pRB-猫眼课题宝

DOI：

10.1016/j.febslet.2006.02.029

发表时间：

2006-03

期刊：

FEBS Letters

影响因子：

3.5

通讯作者：

中科院分区：

生物学3区

文献类型：

--

作者：

C. Uchida;S. Miwa;Tomoyasu Isobe;K. Kitagawa;T. Hattori;T. Oda;H. Yasuda;M. Kitagawa

Mdm 2是一种环指型泛素连接酶，在多种人类癌症中过表达。它促进肿瘤抑制因子p53的泛素化，并可通过在很大程度上下调p53而作为癌基因发挥作用。最近，我们报道了Mdm 2通过泛素-蛋白酶体系统降解视网膜母细胞瘤肿瘤抑制蛋白（pRB）。在本研究中，我们评估了MdmX（Mdm 2的结构同源物）对Mdm 2介导的pRB泛素化的影响。已知MdmX通过增强Mdm 2介导的p53的泛素化和降解来负调节p53功能。有趣的是，MdmX抑制Mdm 2介导的pRB泛素化。此外，MdmX siRNA降低了内源性pRB水平，而MdmX过表达刺激了培养细胞中的pRB功能。因此，MdmX可能在调节Mdm 2对pRB和p53的泛素化活性中具有不同的作用。

Mdm2, a RING-finger type ubiquitin ligase, is overexpressed in a variety of human cancers. It promotes ubiquitination of the tumor suppressor p53 and can function as an oncogene by largely downregulating p53. Recently, we reported that Mdm2 degrades retinoblastoma tumor suppressor protein (pRB) via the ubiquitin–proteasome system. In the present study, we assessed the effects of MdmX, a structural homolog of Mdm2, on the Mdm2-mediated ubiquitination of pRB. MdmX is known to negatively regulate p53 function by enhancing the Mdm2-mediated ubiquitination and degradation of p53. Interestingly, MdmX inhibited the Mdm2-mediated pRB ubiquitination. Furthermore, an MdmX siRNA decreased the endogenous pRB level, while MdmX overexpression stimulated pRB functions in cultured cells. Therefore, MdmX may have different roles in the regulation of Mdm2 activity for ubiquitination of pRB and p53.