Siah1/SIP regulates p27kip1 stability and cell migration under metabolic stress |
| |
| Authors: | Yoshito Nagano Toru Fukushima Kazuo Okemoto Keiichiro Tanaka David DL Bowtell Ze'ev A Ronai John C Reed Shu-ichi Matsuzawa |
| |
| Institution: | 1.Sanford-Burnham Medical Research Institute; La Jolla, CA USA;2.Peter MacCallum Cancer Centre; Department of Research; Cancer Genomics and Biochemistry Laboratory; VIC Australia;3.University of Melbourne; Department of Biochemistry and Molecular Biology; Melbourne, VIC Australia |
| |
| Abstract: | p27kip1 has been implicated in cell cycle regulation, functioning as an inhibitor of cyclin-dependent kinase activity. In addition, p27 was also shown to affect cell migration, with accumulation of cytoplasmic p27 associated with tumor invasiveness. However, the mechanism underlying p27 regulation as a cytoplasmic protein is poorly understood. Here we show that glucose starvation induces proteasome-dependent degradation of cytoplasmic p27, accompanied by a decrease in cell motility. We also show that the glucose limitation-induced p27 degradation is regulated through an ubiquitin E3 ligase complex involving Siah1 and SIP/CacyBP. SIP−/− embryonic fibroblasts have increased levels of cytosolic p27 and exhibit increased cell motility compared with wild-type cells. These observations suggest that the Siah1/SIP E3 ligase complex regulates cell motility through degradation of p27.Key words: p27kip1, Siah1, SIP, glucose starvation, cell migration |
| |
| Keywords: | |
|
|
