PIASxα ligase enhances SUMO1 modification of PTEN protein as a SUMO E3 ligase.

The Journal of Biological Chemistry
Weibin WangXiaowei Zhang

Abstract

The tumor suppressor PTEN plays a critical role in the regulation of multiple cellular processes that include survival, cell cycle, proliferation, and apoptosis. PTEN is frequently mutated or deleted in various human cancer cells to promote tumorigenesis. PTEN is regulated by SUMOylation, but the SUMO E3 ligase involved in the SUMOylation of PTEN remains unclear. Here, we demonstrated that PIASxα is a SUMO E3 ligase for PTEN. PIASxα physically interacted with PTEN both in vitro and in vivo. Their interaction depended on the integrity of phosphatase and C2 domains of PTEN and the region of PIASxα comprising residues 134-347. PIASxα enhanced PTEN protein stability by reducing PTEN ubiquitination, whereas the mutation of PTEN SUMO1 conjugation sites neutralized the effect of PIASxα on PTEN protein half-life. Functionally, PIASxα, as a potential tumor suppressor, negatively regulated the PI3K-Akt pathway through stabilizing PTEN protein. Overexpression of PIASxα led to G0/G1 cell cycle arrest, thus triggering cell proliferation inhibition and tumor suppression, whereas PIASxα knockdown or deficiency in catalytic activity abolished the inhibition. Together our studies suggest that PIASxα is a novel SUMO E3 ligase for PTEN, and it po...Continue Reading

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Citations

Mar 4, 2015·International Journal of Molecular Sciences·Zhenbang Chen, Wenfu Lu
Nov 20, 2015·Nature Communications·Cheng ChenJianxiu Yu
Sep 28, 2018·Cancer Biology & Therapy·Mei Wang, Xiaodong Jiang
Jan 15, 2020·Cold Spring Harbor Perspectives in Medicine·Larissa KotelevetsMark G H Scott
Feb 28, 2018·International Journal of Oncology·Zhi-Jian HanHao Chen
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Jun 25, 2020·Signal Transduction and Targeted Therapy·Liwen ZhouTiebang Kang
Aug 7, 2021·Biomolecules·Iman F Fergani, Luciana R Frick
Sep 1, 2021·Cancer Letters·Yishu Wang, Jianxiu Yu

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