Insulin Increases Sestrin 2 Content by Reducing Its Degradation through the PI 3 K/mTOR Signaling Pathway

International Journal of Endocrinology
Dandan ChaiZhiwen Yu

Abstract

Sestrin (SESN) is known as a cysteine sulfinic acid reductase. Recently, nonredox functions of SESN in metabolic regulation and antitumor property have been recognized. While mechanisms underlying the expression of SESN are not fully understood. Here we report that insulin markedly increased SESN2 level in HepG2 cells through mTOR activation. To determine whether insulin affects SESN2 degradation, we assessed SESN2 turnover by applying the protein synthesis inhibitor, cycloheximide (CHX), and found that following insulin treatment SESN2 protein levels were reduced significantly slower than non-insulin-treated cells. Furthermore, the proteasomal inhibitor, MG132, dramatically increased SESN2 protein and its ubiquitination level while in the presence of MG132 insulin did not further increase SESN2 content, suggesting that insulin increases SESN2 content mainly via inhibiting its proteasomal degradation. We then explored the potential feedback role of SESN2 in insulin signaling by SESN2 siRNA knockdown in HepG2 cells. Following SESN2 knockdown insulin-stimulated PKB phosphorylation was enhanced and accompanied by reduced PTEN content. Taken together, our study suggests that insulin upregulates SESN2 content via the PI3K/mTOR signa...Continue Reading

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Citations

May 7, 2015·Expert Opinion on Therapeutic Targets·Xiaocheng Charlie Dong
Sep 6, 2020·Molecular Biology Reports·Ashish KumarChandrima Shaha
Jul 12, 2017·Oxidative Medicine and Cellular Longevity·Mazhar PashaShankar Munusamy
Dec 24, 2019·Frontiers in Immunology·Li-Xue WangYong-Ming Yao
Dec 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jie Wang BJunlian Gu
Oct 29, 2020·Annual Review of Physiology·Myungjin KimJun Hee Lee
Jun 15, 2021·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Ran SawaYasuhiko Okimura

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Methods Mentioned

BETA
immunoprecipitation
ubiquitination
transfection

Software Mentioned

Quantity One

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