2. Academic Validation
  3. The deubiquitinating enzyme USP20 regulates the stability of the MCL1 protein

The deubiquitinating enzyme USP20 regulates the stability of the MCL1 protein

  • Biochem Biophys Res Commun. 2022 Feb 19:593:122-128. doi: 10.1016/j.bbrc.2022.01.019.
Jinan Feng 1,  Pengyang Liu 2,  Xiaonan Li 3,  Dian Zhang 4,  Hanbin Lin 2,  Zhenzhu Hou 2,  Cairu Guo 5,  Yujie Niu 5,  Bingyu Dai 5,  Ouyang Wang 5,  Min Qi 5,  Huirui Wang 6,  Haitao Zhou 7
Affiliations

Affiliations

  • 1 Department of Central Laboratory, Luoyang Central Hospital Affiliated to Zhengzhou University, Xigong District, Luoyang, Henan, China; The School of Basic Medical Sciences, Fujian Medical University, Minhou, Fuzhou, China. Electronic address: [email protected].
  • 2 The School of Basic Medical Sciences, Fujian Medical University, Minhou, Fuzhou, China.
  • 3 School of Graduate, Xinxiang Medical University, Xinxiang, Henan, China.
  • 4 Department of Thoracic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Xigong District, Luoyang, China.
  • 5 Department of Central Laboratory, Luoyang Central Hospital Affiliated to Zhengzhou University, Xigong District, Luoyang, Henan, China.
  • 6 Department of Central Laboratory, Luoyang Central Hospital Affiliated to Zhengzhou University, Xigong District, Luoyang, Henan, China; School of Graduate, Xinxiang Medical University, Xinxiang, Henan, China.
  • 7 Department of Central Laboratory, Luoyang Central Hospital Affiliated to Zhengzhou University, Xigong District, Luoyang, Henan, China. Electronic address: [email protected].
PMID: 35063767 DOI: 10.1016/j.bbrc.2022.01.019
Abstract

Chemoresistance is a major obstacle faced by oesophageal Cancer patients and is synonymous with a poor prognosis. MCL1 is a pivotal member of the anti-apoptotic Bcl-2 protein family, which has been found to play an important role in cell survival, proliferation, differentiation and chemoresistance. Thus, it might be an ideal target for treating oesophageal Cancer patients. Although it is known that MCL1 is degraded via the ubiquitin-proteasome system, the deubiquitylating enzyme (DUB) responsible for stabilizing MCL1 remains elusive to date. Herein, we demonstrate that Ubiquitin-Specific Protease 20 (USP20) is a novel regulator of the apoptotic signaling pathway. Moreover, USP20 could regulate the deubiquitination of MCL1 to, in turn, regulate its stability. Increased expression of USP20 was correlated with increased levels of MCL1 protein in human patient samples. In addition, depletion of USP20 could increase the polyubiquitination of MCL1, thereby increasing the conversion rate of MCL1 and the sensitivity of cells to chemotherapy. Overall, our findings indicate that the USP20-MCL1 axis might play a key role in the apoptotic signaling pathway.

Keywords

Chemoresistance; Deubiquitinating enzyme; MCL1; Oesophageal cancer; USP20.

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