HAUSP是一种针对p53的去泛素化酶，会发生多聚泛素化、多聚NEDD化及二聚化。

HAUSP, a deubiquitinating enzyme for p53, is polyubiquitinated, polyneddylated, and dimerized.

作者信息

Lee Hye-Jin, Kim Myung-Sun, Kim Yu-Kyung, Oh Yu-Kyoung, Baek Kwang-Hyun

机构信息

Graduate School of Life Science and Biotechnology, Cell and Gene Therapy Research Institute, Pochon CHA University, CHA General Hospital, 605 Yeoksam 1-dong, Kangnam-Gu, Seoul 135-081, Korea.

出版信息

FEBS Lett. 2005 Aug 29;579(21):4867-72. doi: 10.1016/j.febslet.2005.07.048.

DOI:10.1016/j.febslet.2005.07.048

PMID:16111684

Abstract

The tumor suppressor protein p53 is ubiquitinated and neddylated by MDM2 and then degraded by 26S proteasome. However, p53 is stabilized by the HAUSP (Herpes-virus-associated ubiquitin-specific protease) deubiquitinating enzyme. In this study, we discovered that rat HAUSP (rHAUSP) is polyubiquitinated, polyneddylated, and dimerized using co-immunoprecipitation assays. This suggests that rHAUSP may function as a dimer or multimer and is also degraded through the proteasome-mediated degradation. Transfection of rHAUSP into RGC-Lac-Z cell line with the integrated p53 response element revealed that rHAUSP contributed to p53 stabilization, and a rHAUSP (C224S) mutant contributed to p53 destabilization in a dose-dependent manner.

摘要

肿瘤抑制蛋白p53被MDM2泛素化和NEDD化，然后被26S蛋白酶体降解。然而，p53可被HAUSP（疱疹病毒相关泛素特异性蛋白酶）去泛素化酶稳定。在本研究中，我们通过免疫共沉淀实验发现大鼠HAUSP（rHAUSP）被多聚泛素化、多聚NEDD化并二聚化。这表明rHAUSP可能以二聚体或多聚体形式发挥作用，并且也通过蛋白酶体介导的降解途径被降解。将rHAUSP转染到整合有p53反应元件的RGC-Lac-Z细胞系中发现，rHAUSP有助于p53的稳定，而rHAUSP（C224S）突变体则以剂量依赖的方式导致p53不稳定。