The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1
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 E...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | Biochemistry Research International |
| Online Access: | http://dx.doi.org/10.1155/2012/282648 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832567507505905664 |
|---|---|
| author | Christine Zhiwen Hu Jaswinder K. Sethi Thilo Hagen |
| author_facet | Christine Zhiwen Hu Jaswinder K. Sethi Thilo Hagen |
| author_sort | Christine Zhiwen Hu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4203beaa53fc4f5cbd96dc324629dcf0 |
| institution | Kabale University |
| issn | 2090-2247 2090-2255 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Biochemistry Research International |
| spelling | doaj-art-4203beaa53fc4f5cbd96dc324629dcf02025-02-03T01:01:18ZengWileyBiochemistry Research International2090-22472090-22552012-01-01201210.1155/2012/282648282648The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1Christine Zhiwen Hu0Jaswinder K. Sethi1Thilo Hagen2Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeInstitute of Metabolic Science, Metabolic Research Laboratories, and Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB20QQ, UKDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeBackground. 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.http://dx.doi.org/10.1155/2012/282648 |
| spellingShingle | Christine Zhiwen Hu Jaswinder K. Sethi Thilo Hagen The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1 Biochemistry Research International |
| title | The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1 |
| title_full | The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1 |
| title_fullStr | The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1 |
| title_full_unstemmed | The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1 |
| title_short | The Role of the Cullin-5 E3 Ubiquitin Ligase in the Regulation of Insulin Receptor Substrate-1 |
| title_sort | role of the cullin 5 e3 ubiquitin ligase in the regulation of insulin receptor substrate 1 |
| url | http://dx.doi.org/10.1155/2012/282648 |
| work_keys_str_mv | AT christinezhiwenhu theroleofthecullin5e3ubiquitinligaseintheregulationofinsulinreceptorsubstrate1 AT jaswinderksethi theroleofthecullin5e3ubiquitinligaseintheregulationofinsulinreceptorsubstrate1 AT thilohagen theroleofthecullin5e3ubiquitinligaseintheregulationofinsulinreceptorsubstrate1 AT christinezhiwenhu roleofthecullin5e3ubiquitinligaseintheregulationofinsulinreceptorsubstrate1 AT jaswinderksethi roleofthecullin5e3ubiquitinligaseintheregulationofinsulinreceptorsubstrate1 AT thilohagen roleofthecullin5e3ubiquitinligaseintheregulationofinsulinreceptorsubstrate1 |