The deubiquitinating protein USP24 interacts with DDB2 and regulates DDB2 stability |
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Authors: | Ling Zhang Abigail Lubin Hua Chen Zhongyi Sun Feng Gong |
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Affiliation: | 1.Department of Biochemistry and Molecular Biology; Miller School of Medicine; University of Miami; Miami, FL USA;2.Department of Urology; Research Institute of Surgery; Daping Hospital; Third Military Medical University; Chongqing, China |
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Abstract: | Damage-specific DNA-binding protein 2 (DDB2) was first isolated as a subunit of the UV-DDB heterodimeric complex that is involved in DNA damage recognition in the nucleotide excision repair pathway (NER). DDB2 is required for efficient repair of CPDs in chromatin and is a component of the CRL4DDB2 E3 ligase that targets XPC, histones and DDB2 itself for ubiquitination. In this study, a yeast two-hybrid screening of a human cDNA library was performed to identify potential DDB2 cellular partners. We identified a deubiquitinating enzyme, USP24, as a likely DDB2-interacting partner. Interaction between DDB2 and USP24 was confirmed by co-precipitation. Importantly, knockdown of USP24 in two human cell lines decreased the steady-state levels of DDB2, indicating that USP24-mediated DDB2 deubiquitination prevents DDB2 degradation. In addition, we demonstrated that USP24 can cleave an ubiquitinated form of DDB2 in vitro. Taken together, our results suggest that the ubiquitin-specific protease USP24 is a novel regulator of DDB2 stability. |
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Keywords: | DDB2 UV-DDB nucleotide excision repair yeast two-hybrid USP24 deubiquitination deubiquitinase XPE |
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