Abstract：
Dysfunction of the tumor suppressor p53 occurs in most human cancers, Hdm2 and HdmX play critical roles in p53 inactivation and degradation. Under unstressed conditions, HdmX binds to p53 like Hdm2, but HdmX cannot directly induce p53 degradation. Moreover, HdmX has been reported to stimulate Hdm2-mediated ubiquitination and degradation of p53. Here we reported that HdmX promoted the nuclear export of p53 independent of Hdm2 in living cells using FRET technology. Whereas, Hdm2 impeded HdmX-mediated nuclear export of p53 by sequestering it in nucleus. Interestingly, the C-terminal RING domain mutant Hdm2C464A formed heterooligomers with p53 in nucleus, which was inhibited by HdmX. The heterooligomers were located near PML-NBs. This study indicate that the nuclear Hdm2-HdmX interaction aborts the HdmX-mediated nuclear export of p53.
摘要：
肿瘤抑制因子p53的功能障碍发生在大多数人类癌症中，Hdm2和HdmX在p53失活和降解中起关键作用。在无压力条件下，HdmX像Hdm2一样与p53结合,但HdmX不能直接诱导p53降解。此外，已报道HdmX刺激Hdm2介导的p53的泛素化和降解。在这里，我们报道了使用FRET技术，HdmX促进了活细胞中独立于Hdm2的p53核输出。然而,Hdm2通过将其隔离在细胞核中来阻碍HdmX介导的p53的核输出。有趣的是,C端RING结构域突变体Hdm2C464A在细胞核中形成与p53的异源寡聚体，被HdmX抑制。杂低聚物位于PML-NBs附近。这项研究表明，核Hdm2-HdmX相互作用中止了HdmX介导的p53核输出。
