Deubiquitylation and stabilization of PTEN by USP13

Jinsong Zhang, Peijing Zhang, Yongkun Wei, Hai Long Piao, Wenqi Wang, Subbareddy Maddika, Min Wang, Dahu Chen, Yutong Sun, Mien Chie Hung, Junjie Chen, Li Ma

Research output: Contribution to journalArticle

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Abstract

The tumour suppressor PTEN is frequently lost in human cancers. In addition to gene mutations and deletions, recent studies have revealed the importance of post-translational modifications, such as ubiquitylation, in the regulation of PTEN stability, activity and localization. However, the deubiquitylase that regulates PTEN polyubiquitylation and protein stability remains unknown. Here we screened a total of 30 deubiquitylating enzymes (DUBs) and identified five DUBs that physically associate with PTEN. One of them, USP13, stabilizes the PTEN protein through direct binding and deubiquitylation of PTEN. Loss of USP13 in breast cancer cells promotes AKT phosphorylation, cell proliferation, anchorage-independent growth, glycolysis and tumour growth through downregulation of PTEN. Conversely, overexpression of USP13 suppresses tumorigenesis and glycolysis in PTEN-positive but not PTEN-null breast cancer cells. Importantly, USP13 protein is downregulated in human breast tumours and correlates with PTEN protein levels. These findings identify USP13 as a tumour-suppressing protein that functions through deubiquitylation and stabilization of PTEN.

Original languageEnglish (US)
Pages (from-to)1486-1494
Number of pages9
JournalNature cell biology
Volume15
Issue number12
DOIs
StatePublished - Dec 2013

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PTEN Phosphohydrolase
Glycolysis
Breast Neoplasms
Neoplasms
Down-Regulation
Protein Stability
Ubiquitination
Gene Deletion
Post Translational Protein Processing
Growth
Carcinogenesis
Proteins
Phosphorylation
Cell Proliferation
Mutation
Enzymes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Zhang, J., Zhang, P., Wei, Y., Piao, H. L., Wang, W., Maddika, S., ... Ma, L. (2013). Deubiquitylation and stabilization of PTEN by USP13. Nature cell biology, 15(12), 1486-1494. https://doi.org/10.1038/ncb2874

Deubiquitylation and stabilization of PTEN by USP13. / Zhang, Jinsong; Zhang, Peijing; Wei, Yongkun; Piao, Hai Long; Wang, Wenqi; Maddika, Subbareddy; Wang, Min; Chen, Dahu; Sun, Yutong; Hung, Mien Chie; Chen, Junjie; Ma, Li.

In: Nature cell biology, Vol. 15, No. 12, 12.2013, p. 1486-1494.

Research output: Contribution to journalArticle

Zhang, J, Zhang, P, Wei, Y, Piao, HL, Wang, W, Maddika, S, Wang, M, Chen, D, Sun, Y, Hung, MC, Chen, J & Ma, L 2013, 'Deubiquitylation and stabilization of PTEN by USP13', Nature cell biology, vol. 15, no. 12, pp. 1486-1494. https://doi.org/10.1038/ncb2874
Zhang J, Zhang P, Wei Y, Piao HL, Wang W, Maddika S et al. Deubiquitylation and stabilization of PTEN by USP13. Nature cell biology. 2013 Dec;15(12):1486-1494. https://doi.org/10.1038/ncb2874
Zhang, Jinsong ; Zhang, Peijing ; Wei, Yongkun ; Piao, Hai Long ; Wang, Wenqi ; Maddika, Subbareddy ; Wang, Min ; Chen, Dahu ; Sun, Yutong ; Hung, Mien Chie ; Chen, Junjie ; Ma, Li. / Deubiquitylation and stabilization of PTEN by USP13. In: Nature cell biology. 2013 ; Vol. 15, No. 12. pp. 1486-1494.
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