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Siah1/SIP regulates p27(kip1) stability and cell migration under metabolic stress.


ABSTRACT: p27(kip1) 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 to wild-type cells. These observations suggest that the Siah1/SIP E3 ligase complex regulates cell motility through degradation of p27.

SUBMITTER: Nagano Y 

PROVIDER: S-EPMC3180198 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Siah1/SIP regulates p27(kip1) stability and cell migration under metabolic stress.

Nagano Yoshito Y   Fukushima Toru T   Okemoto Kazuo K   Tanaka Keiichiro K   Bowtell David D L DD   Ronai Ze'ev Z   Reed John C JC   Matsuzawa Shu-ichi S  

Cell cycle (Georgetown, Tex.) 20110801 15


p27(kip1) 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 sh  ...[more]

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