Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth

Nan Li, Yajie Zhang, Xin Han, Ke Liang, Jiadong Wang, Lin Feng, Wenqi Wang, Zhou Songyang, Chunru Lin, Liuqing Yang, Yonghao Yu, Junjie Chen

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

PTEN [phosphatidylinositol (3,4,5)-trisphosphate phosphatase and tensin homolog deleted from chromosome 10], a phosphatase and critical tumor suppressor, is regulated by numerous post-translational modifications, including phosphorylation, ubiquitination, acetylation, and SUMOylation, which affect PTEN localization and protein stability. Here we report ADP-ribosylation as a new post-translational modification of PTEN. We identified PTEN as a novel substrate of tankyrases, which are members of the poly(ADP-ribose) polymerases (PARPs). We showed that tankyrases interact with and ribosylate PTEN, which promotes the recognition of PTEN by a PAR-binding E3 ubiquitin ligase, RNF146, leading to PTEN ubiquitination and degradation. Double knockdown of tankyrase1/2 stabilized PTEN, resulting in the subsequent down-regulation of AKT phosphorylation and thus suppressed cell proliferation and glycolysis in vitro and tumor growth in vivo. Furthermore, tankyrases were up-regulated and negatively correlated with PTEN expression in human colon carcinomas. Together, our study revealed a new regulation of PTEN and highlighted a role for tankyrases in the PTEN-AKT pathway that can be explored further for cancer treatment.

Original languageEnglish (US)
Pages (from-to)157-170
Number of pages14
JournalGenes and Development
Volume29
Issue number2
DOIs
StatePublished - Jan 15 2015

Fingerprint

Tankyrases
Adenosine Diphosphate
Ubiquitination
Post Translational Protein Processing
Growth
Phosphoric Monoester Hydrolases
Neoplasms
Phosphorylation
PTEN Phosphohydrolase
Sumoylation
Chromosomes, Human, Pair 10
Ubiquitin-Protein Ligases
Poly(ADP-ribose) Polymerases
Protein Stability
Glycolysis
Acetylation
Colon
Down-Regulation
Cell Proliferation
Carcinoma

Keywords

  • PARsylation
  • PTEN
  • RNF146
  • Tankyrase
  • Ubiquitination

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Li, N., Zhang, Y., Han, X., Liang, K., Wang, J., Feng, L., ... Chen, J. (2015). Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth. Genes and Development, 29(2), 157-170. https://doi.org/10.1101/gad.251785.114

Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth. / Li, Nan; Zhang, Yajie; Han, Xin; Liang, Ke; Wang, Jiadong; Feng, Lin; Wang, Wenqi; Songyang, Zhou; Lin, Chunru; Yang, Liuqing; Yu, Yonghao; Chen, Junjie.

In: Genes and Development, Vol. 29, No. 2, 15.01.2015, p. 157-170.

Research output: Contribution to journalArticle

Li, N, Zhang, Y, Han, X, Liang, K, Wang, J, Feng, L, Wang, W, Songyang, Z, Lin, C, Yang, L, Yu, Y & Chen, J 2015, 'Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth', Genes and Development, vol. 29, no. 2, pp. 157-170. https://doi.org/10.1101/gad.251785.114
Li, Nan ; Zhang, Yajie ; Han, Xin ; Liang, Ke ; Wang, Jiadong ; Feng, Lin ; Wang, Wenqi ; Songyang, Zhou ; Lin, Chunru ; Yang, Liuqing ; Yu, Yonghao ; Chen, Junjie. / Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth. In: Genes and Development. 2015 ; Vol. 29, No. 2. pp. 157-170.
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