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Siah1/SIP regulates p27(kip1) stability and cell migration under metabolic stress.
- Source :
-
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2011 Aug 01; Vol. 10 (15), pp. 2592-602. Date of Electronic Publication: 2011 Aug 01. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
Calcium-Binding Proteins deficiency
Calcium-Binding Proteins genetics
Cell Line
Cell Movement
Glucose metabolism
Glucose pharmacology
Humans
Interphase
Mice
Proteasome Endopeptidase Complex metabolism
Calcium-Binding Proteins metabolism
Cyclin-Dependent Kinase Inhibitor p27 metabolism
Nuclear Proteins metabolism
Stress, Physiological
Ubiquitin-Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1551-4005
- Volume :
- 10
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Cell cycle (Georgetown, Tex.)
- Publication Type :
- Academic Journal
- Accession number :
- 21734459
- Full Text :
- https://doi.org/10.4161/cc.10.15.16912