2. Academic Validation
  3. TRABID targets DDB2 for deubiquitination to promote proliferation of hepatocellular carcinoma cells

TRABID targets DDB2 for deubiquitination to promote proliferation of hepatocellular carcinoma cells

  • Biochem Biophys Res Commun. 2022 Oct 15:625:23-30. doi: 10.1016/j.bbrc.2022.07.109.
Yaping Chen 1,  Xiaofei Zhang 2
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China.
  • 2 CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: [email protected].
PMID: 35944360 DOI: 10.1016/j.bbrc.2022.07.109
Abstract

TRAF-binding domain-containing protein (TRABID), a member of the OTU Deubiquitinase family, has an important role in regulating cellular functions via deubiquitinating substrate proteins such as EZH2 and Jmjd2d. However, the mechanism of its role in the proliferation of hepatocellular carcinoma (HCC) cells has not been fully elucidated. Here, we analyzed the interactome of TRABID in HepG2 cells through mass spectrometry-based proteomics and found that TRABID is associated with damaged DNA-binding protein2 (DDB2). Immunoprecipitation assay showed that the interaction of TRABID and DDB2 is mediated by their OTU domain and N-terminal region, respectively. Furthermore, TRABID deubiquitinates DDB2, and this deubiquitination effect of TRABID depends on its active site. Functionally, we showed that TRABID-mediated hepatocellular carcinoma cell proliferation is attenuated by DDB2 knockdown. Thus, our data revealed a critical role of the TRABID-DDB2 axis in the proliferation of hepatocellular carcinoma cells.

Keywords

DDB2; Deubiquitination; Hepatocellular carcinoma; TRABID.

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