SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane

Huang, Jian; Yan, Jie; Zhang, Jian; Zhu, Shuchai; Wang, Yanli; Shi, Ting; Zhu, Changhong; Cheng, Chen; Liu, Xin; Cheng, Jinke; Mustelin, Tomas; Feng, Gen‐Sheng; Chen, Guoqiang; Yu, Jianxiu

doi:10.1038/ncomms1919

Cited by 174 publications

(211 citation statements)

References 43 publications

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“…SUMOylation of K266 is closely related to PTEN membrane localization, whereby it facilitates PTEN binding to the plasma membrane. 36 SUMOylation of PTEN K254 regulates its nuclear localization. After exposure to genotoxic stress, SUMO-PTEN was rapidly excluded from the nucleus, and this process depended on the phosphorylation of PTEN T398 by ataxia telangiectasia mutated.…”

Section: Regulation Of Pten Functionsmentioning

confidence: 99%

The functions of tumor suppressor PTEN in innate and adaptive immunity

Chen

Guo

2017

Cell Mol Immunol

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The tumor suppressor phosphatase and tensin homolog (PTEN) is a lipid and protein phosphatase that is able to antagonize the PI3K/AKT pathway and inhibit tumor growth. PTEN also possesses phosphatase-independent functions. Genetic alterations of PTEN may lead to the deregulation of cell proliferation, survival, differentiation, energy metabolism and cellular architecture and mobility. Although the role of PTEN in tumor suppression is extensively documented and well established, the evidence for its roles in immunity did not start to accumulate until recently. In this review, we will focus on the newly discovered functions of PTEN in the regulation of innate and adaptive immunity, including antiviral responses.

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Section: Regulation Of Pten Functionsmentioning

confidence: 99%

The functions of tumor suppressor PTEN in innate and adaptive immunity

Chen

Guo

2017

Cell Mol Immunol

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“…As an important regulator of many cellular processes, it is not surprising that PTEN is subjected to a variety of post-translational modifications that regulate its phosphatase activity as well as its subcellular localization. These modifications include phosphorylation (Torres and Pulido 2001), ubiquitination (Wang et al 2007;Maddika et al 2011), acetylation (Okumura et al 2006), oxidation (Kwon et al 2004), and SUMOylation (Huang et al 2012;Bassi et al 2013).…”

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confidence: 99%

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

Zhang

Han³

et al. 2014

Genes Dev.

114

126

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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.

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“…Different laboratories have described recently that SUMO conjugation to PTEN regulates its subcellular distribution and activity. [53][54][55] In this context, it seems that the emerging concept of "group SUMOylation", which refers to the requirement for simultaneous modification of multiple targets involved in the same biological process, 4,56 could apply to the regulation of the Pi3K-Akt signaling axis.…”

Section: Discussionmentioning

confidence: 99%