Journal Article

USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization

Yang, Fuquan, Ding, Xiang, Zhang, Qi, Liu, Ling, Cao, Cheng, Tian, Shanshan, Yu, Na, Wu, Shaoyuan, Sun, Tao, Yao, Zhi, Song, Nan, Zhang, Kai, Yang, Shangda, Ma, Shuai, Yang, Jie, Shi, Lei, Wang, Yuejiao

2018

Overview

Histone chaperone ASF1A has been reported to be dysregulated in multiple tumors; however, the underlying molecular mechanism that how the abundance and function of ASF1A are regulated remains unclear. Here we report that ASF1A is physically associated with USP52, which is previously identified as a pseudo-deubiquitinase. Interestingly, we demonstrate that USP52 is a bona fide ubiquitin-specific protease, and USP52 promotes ASF1A deubiquitination and stabilization. USP52-promoted ASF1A stabilization facilitates chromatin assembly and favors cell cycle progression. Additionally, we find that USP52 is overexpressed in breast carcinomas, and its level of expression correlates with that of ASF1A. Moreover, we reveal that impairment of USP52-promoted ASF1A stabilization results in growth arrest of breast cancer cells and sensitizes these cells to DNA damage. Our experiments identify USP52 as a truly protein deubiquitinase, uncover a molecular mechanism of USP52 in chromatin assembly, and reveal a potential role of USP52 in breast carcinogenesis. Histone chaperone ASF1A is often dysregulated in cancers, however the regulation of its abundance is unclear. Here, the authors show that USP52 promotes ASF1A stability through deubiquitination while impairment of this stability reduces breast tumorigenesis and confers sensitivity to DNA damage.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/109 / 13/51 / 13/89 / 14 / 14/19 / 631/337/458/582 / 692/4028/67/1347 / 82/1 / 82/58 / 82/83 / 96/106 / 96/31 / Animals / Assembly / Breast cancer / Breast carcinoma / Breast Neoplasms - pathology / Carcinogenesis / Carcinogens / Cell cycle / Cell Cycle Proteins - metabolism / Cell Line, Tumor / Chromatin / Chromatin remodeling / Damage detection / Deoxyribonucleic acid / Deubiquitinating Enzymes - metabolism / DNA / DNA damage / Exoribonucleases - metabolism / Female / HCT116 Cells / HEK293 Cells / HeLa Cells / Humanities and Social Sciences / Humans / MCF-7 Cells / Mice / Mice, Inbred BALB C / Mice, Nude / Molecular Chaperones - metabolism / multidisciplinary / Neoplasm Transplantation / RNA Interference / RNA, Small Interfering - genetics / Science / Science (multidisciplinary) / Sf9 Cells / Spodoptera / Stabilization / Transplantation, Heterologous / Tumors / Ubiquitin / Ubiquitin-specific proteinase