The ubiquitin-proteasome pathway is a new partner for the... : Current Opinion in Clinical Nutrition & Metabolic Care (original) (raw)

Anabolic and catabolic signals

The ubiquitin-proteasome pathway is a new partner for the control of insulin signaling

UMR INRA1235-INSERM 449, Mécanismes moléculaires du diabète, Faculté de Médecine Laënnec, 69008 Lyon, France

Correspondence to Sophie Rome, UMR INRA1235-INSERM 449, Mécanismes moléculaires du diabète, Faculté de Médecine Laënnec, 69008 Lyon, France Tel: +33 4 78 77 10 46; fax: +33 4 78 77 89 62; e-mail: [email protected]

Abbreviations

IDE: insulin-degrading enzyme

IRS: insulin receptor substrate

PI3-K: phosphatidylinositol 3-kinase

PKB: protein kinase B

PPAR: peroxisome proliferator-activated receptor

SOCS: suppressor of cytokine signaling

SREBP: sterol regulatory element-binding protein

Abstract

Purpose of review

Insulin signaling is a transitory effect that has to be tightly controlled in magnitude and duration in order to maintain cell homeostasis. Recent reports have demonstrated that members of the ubiquitin-proteasome pathway represent new partners that have to be taken into account for the regulation of insulin action.

Recent findings

The protein amounts of the different signaling molecules involved in insulin action are regulated by their rates of synthesis and degradation. The ubiquitin-proteasome system is involved in the internalization of the insulin receptor, in the control of the amount of insulin receptor substrates 1 and 2, and in insulin degradation. Finally, ubiquitination and sumoylation regulate transcription factors and nuclear receptors that mediate insulin-induced gene expression.

Summary

It is well known from transgenic models that inappropriate levels of signaling molecules strongly affect insulin action. In humans also, several reports have provided evidence of altered levels of key proteins involved in insulin action in pathologies such as type 2 diabetes. The relationship between these abnormalities and the ubiquitin-proteasome pathway has yet to be clarified, but clarifying the role of ubiquitination in insulin action will certainly lead to a better understanding of insulin resistance.