Table of Contents Author Guidelines Submit a Manuscript
Biochemistry Research International
Volume 2012 (2012), Article ID 282648, 8 pages
Research Article

The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1

1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
2Institute of Metabolic Science, Metabolic Research Laboratories, and Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB20QQ, UK

Received 17 July 2012; Revised 2 November 2012; Accepted 11 November 2012

Academic Editor: Emil Pai

Copyright © 2012 Christine Zhiwen Hu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. SOCS proteins are known to negatively regulate insulin signaling by inhibiting insulin receptor substrate-1 (IRS1). IRS1 has been reported to be a substrate for ubiquitin-dependent proteasomal degradation. Given that SOCS proteins can function as substrate receptor subunits of Cullin-5 E3 ubiquitin ligases, we examined whether Cullin-5 dependent ubiquitination is involved in the regulation of basal IRS1 protein stability and signal-induced IRS1 degradation. Findings. Our results indicate that basal IRS1 stability varies between cell types. However, the Cullin-5 E3 ligase does not play a major role in mediating IRS1 ubiquitination under basal conditions. Protein kinase C activation triggered pronounced IRS1 destabilization. However, this effect was also independent of the function of Cullin-5 E3 ubiquitin ligases. Conclusions. In conclusion, SOCS proteins do not exert a negative regulatory effect on IRS1 by functioning as substrate receptors for Cullin-5-based E3 ubiquitin ligases both under basal conditions and when IRS1 degradation is induced by protein kinase C activation.