USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization
| Autor: | Shuai Ma, Zhang Qi, Tao Sun, Zhi Yao, Fuquan Yang, Shaoyuan Wu, Kai Zhang, Na Yu, Cheng Cao, Shanshan Tian, Yuejiao Wang, Lei Shi, Xiang Ding, Shangda Yang, Jie Yang, Nan Song, Ling Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
DNA damage Science Transplantation Heterologous General Physics and Astronomy Mice Nude Breast Neoplasms Cell Cycle Proteins Spodoptera General Biochemistry Genetics and Molecular Biology Article Deubiquitinating enzyme 03 medical and health sciences Mice RNA interference Cell Line Tumor Sf9 Cells Animals Humans RNA Small Interfering lcsh:Science Mice Inbred BALB C Multidisciplinary biology Deubiquitinating Enzymes Chemistry HEK 293 cells General Chemistry HCT116 Cells Cell biology Transplantation 030104 developmental biology Histone HEK293 Cells Chaperone (protein) Exoribonucleases biology.protein MCF-7 Cells lcsh:Q Female RNA Interference Neoplasm Transplantation Deubiquitination HeLa Cells Molecular Chaperones |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-17 (2018) |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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