Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, China.
J Mol Neurosci. 2012 Jan;46(1):184-91. doi: 10.1007/s12031-011-9572-9. Epub 2011 Jul 5.
Pirh2, a p53-induced ubiquitin-protein ligase, has been reported to promote ubiquitin-dependent degradation of p27(kip1), which plays an essential role in mammalian cell cycle regulation and neurogenesis in the developing central nervous system (CNS). However, their distributions and functions in the nervous system lesion and repair remain unclear. In this study, we observed that the up-regulated expression of Pirh2 was concomitant with decreased p27(kip1) level after traumatic brain injury by Western blot and immunohistochemistry. Immunofluorescence double-labeling revealed that Pirh2 was mainly co-expressed with GFAP and CD11b. Meanwhile, we also examined the expression profiles of proliferating cell nuclear antigen (PCNA) whose changes were correlated with the expression of Pirh2. In addition, Pirh2 colocalized with p27(kip1) and PCNA. Immunoprecipitation further showed that they interacted with each other in the pathophysiology process. In summary, our data indicated Pirh2 might be a negative regulator of p27(kip1) and associated with glial proliferation.
Pirh2 是一种 p53 诱导的泛素蛋白连接酶，已被报道可促进 p27(kip1)的泛素依赖性降解，p27(kip1) 在哺乳动物细胞周期调控和发育中中枢神经系统 (CNS) 的神经发生中发挥着重要作用。然而，它们在神经系统损伤和修复中的分布和功能仍不清楚。在这项研究中，我们通过 Western blot 和免疫组织化学观察到创伤性脑损伤后 Pirh2 的表达上调伴随着 p27(kip1)水平的降低。免疫荧光双重标记显示 Pirh2 主要与 GFAP 和 CD11b 共表达。同时，我们还检查了增殖细胞核抗原 (PCNA) 的表达谱，其变化与 Pirh2 的表达相关。此外，Pirh2 与 p27(kip1)和 PCNA 共定位。免疫沉淀进一步表明它们在病理生理学过程中相互作用。总之，我们的数据表明 Pirh2 可能是 p27(kip1)的负调节剂，并与神经胶质细胞增殖有关。
