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The equilibrium of tumor suppression: DUBs as active regulators of PTEN

  • 작성자

    Min Sup Song
  • 작성일자

    2022-12-22
  • 조회수

    323
Min Sup Song( msong1@mdanderson.org )
2020-present Associate Professor, Department of Molecular and Cellular Oncology, MD Anderson Cancer Center, USA
2013-2020 Assistant Professor, Department of Molecular and Cellular Oncology, MD Anderson Cancer Center, USA
2011-2013 Instructor, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, USA
2007-2011 Postdoctoral, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, USA
2001-2007 Postdoctoral, Department of Biological Sciences, Korea Advanced Institute of Sciences and Technologies, Korea
1997-2001 PhD, Division of Life Sciences, College of Life Science & Biotechnology, Korea University, Korea

The equilibrium of tumor suppression: DUBs as active regulators of PTEN

PTEN is among the most commonly lost or mutated tumor suppressor genes in human cancer. PTEN, a bona fide lipid phosphatase that antagonizes the highly oncogenic PI3K-AKT-mTOR pathway, is considered a major dose-dependent tumor suppressor. Although PTEN function can be compromised by genetic mutations in inherited syndromes and cancers, posttranslational modifications of PTEN may also play key roles in the dynamic regulation of its function. Notably, deregulated ubiquitination and deubiquitination lead to detrimental impacts on PTEN levels and subcellular partitioning, promoting tumorigenesis. While PTEN can be targeted by HECT-type E3 ubiquitin ligases for nuclear import and proteasomal degradation, studies have shown that several deubiquitinating enzymes, including HAUSP/USP7, USP10, USP11, USP13, OTUD3 and Ataxin-3, can remove ubiquitin from ubiquitinated PTEN in cancer-specific contexts and thus reverse ubiquitination-mediated PTEN regulation. Researchers continue to reveal the precise molecular mechanisms by which cancer-specific deubiquitinases of PTEN regulate its roles in the pathobiology of cancer, and new methods of pharmacologically for modulating PTEN deubiquitinases are critical areas of investigation for cancer treatment and prevention. Here, we assess the mechanisms and functions of deubiquitination as a recently appreciated mode of PTEN regulation and review the link between deubiquitinases and PTEN reactivation and its implications for therapeutic strategies.

Exp Mol Med. 2022 Nov;54(11):1814-1821. doi: 10.1038/s12276-022-00887-w.
https://pubmed.ncbi.nlm.nih.gov/36385557/