PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through the inhibition of TM4 (UBAC2) degradation.

ABSTRACT:

Background

The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin-proteasome inhibitor PS-341 could regulate the function of TM4.

Methods

The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro.

Results

TM4 KO mice de

SUBMITTER: Chen L 

PROVIDER: S-EPMC8170790 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature