MECHANISMS OF SUBSTRATE DEGRADATION AND RECRUITMENT BY CULLIN E3 LIGASES

Protein degradation plays an important role in regulating many cellular processes. Ubiquitination, a prerequisite for protein degradation, is mediated by the Cullin E3 ubiquitin ligase family. The aim of this study is to achieve a better understanding of the function and regulation of Cullin E3 ligases. We studied the degradation of insulin receptor substrate 1 (IRS1) by the Cullin5 E3 ligase, and found that the basal and signal-induced degradation of IRS1 protein is not dependent on Cullin5. We next investigated the regulation of the Cullin1 E3 ligase substrate receptor module, consisting of the Skp1 adaptor protein and one of the 70 F-box proteins. A model is proposed, whereby the F-box protein dynamically associates with Skp1. Lastly, Skp1a, a splice variant of the commonly-studied Skp1b protein, is characterized for the first time. Our results suggest that Skp1a may have alternate functions from Skp1b.

Author dc:creator

• CHRISTINE HU ZHI WEN

• Protein degradation, Cullin E3 ubiquitin ligases, insulin receptor substrate 1, Skp1, Skp2, F-box proteins