title: 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.
authors: Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors: Yoshito
authors: Y
authors: Nagano
authors: Toru
authors: T
authors: Fukushima
authors: Kazuo
authors: K
authors: Okemoto
authors: Keiichiro
authors: K
authors: Tanaka
authors: David D L
authors: DD
authors: Bowtell
authors: Ze'ev
authors: Z
authors: Ronai
authors: John C
authors: JC
authors: Reed
authors: Shu-ichi
authors: S
authors: Matsuzawa
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007399:Interphase; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013312:Stress, Physiological; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: C111922:Cacybp protein, mouse; D002135:Calcium-Binding Proteins; D009687:Nuclear Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D046988:Proteasome Endopeptidase Complex; D005947:Glucose