1. Academic Validation
  2. USP39 promotes tumorigenesis by stabilizing and deubiquitinating SP1 protein in hepatocellular carcinoma

USP39 promotes tumorigenesis by stabilizing and deubiquitinating SP1 protein in hepatocellular carcinoma

  • Cell Signal. 2021 Sep;85:110068. doi: 10.1016/j.cellsig.2021.110068.
Xiao Dong 1 Zixin Liu 2 Encheng Zhang 3 Pingzhao Zhang 4 Yuqi Wang 4 Junjie Hang 5 Qi Li 6
Affiliations

Affiliations

  • 1 Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China.
  • 2 Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), Shanghai, China.
  • 3 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China.
  • 4 Department of Oncology, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou, China.
  • 5 Department of Oncology, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou, China. Electronic address: hjj199141@alumni.sjtu.edu.cn.
  • 6 Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China. Electronic address: leeqi@sjtu.edu.cn.
Abstract

Deubiquitinating Enzyme (DUB) can hydrolyze ubiquitin molecules from the protein bound with ubiquitin, and reversely regulate protein degradation. The ubiquitin-specific proteases (USP) family are cysteine proteases, which owns the largest members and diverse structure among the currently known DUB. The important roles of ubiquitin-specific peptidase39 (USP39) in Cancer have been widely investigated. However, little is known about the putative de-ubiquitination function of USP39 in hepatocellular carcinoma (HCC) and the mechanisms of USP39 regulating tumor growth. Here, we used bioinformatics methods to reveal that USP39 expression is significantly upregulated in several Cancer database. High expression of USP39 is correlated with poor prognosis of HCC patients. Then, we identify the specificity protein 1 (SP1), as a novel subtract of the USP39. We observe that USP39 stabilizes SP1 protein and prolongs its half-life by promoting its deubiquitylation pathway. In addition, our results show USP39 promotes cell proliferation by SP1-depenet manner in vivo and vitro. Knocking-down of USP39 promotes the cell Apoptosis and arrest of the cell cycle, whereas SP1 forcefully reversed these effects. Taken together, our results suggest that USP39 participates the deubiquitylation of SP1 protein, providing new pathway for understand the upstream signaling for oncogene SP1.

Keywords

De-ubiquitination; Hepatocellular carcinoma; Proliferation; SP1; USP39.

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