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A pathway in quiescent cells that controls p27Kip1 stability, subcellular localization, and tumor suppression.
- Source :
-
Genes & Development . 1/1/2006, Vol. 20 Issue 1, p47-64. 18p. 2 Color Photographs, 1 Diagram, 2 Charts, 6 Graphs. - Publication Year :
- 2006
-
Abstract
- We have created two knock-in mouse models to study the mechanisms that regulate p27 in normal cells and cause misregulation of p27 in tumors: p27S10A, in which Ser10 is mutated to Ala; and p27CK-, in which point mutations abrogate the ability of p27 to bind cyclins and CDKs. These two mutant alleles identify steps in a pathway that controls the proteasomal degradation of p27 uniquely in quiescent cells: Dephosphorylation of p27 on Ser10 inhibits p27 nuclear export and promotes its assembly into cyclin-CDK complexes, which is, in turn, necessary for p27 turnover. We further show that Ras-dependent lung tumorigenesis is associated with increased phosphorylation on Ser10 and cytoplasmic mislocalization of p27. Indeed, we find that p27S10A is refractory to Ras-induced cytoplasmic translocation and that p27S10A mice are tumor resistant. Thus, phosphorylation of p27 on Ser10 is an important event in the regulation of the tumor suppressor function of p27. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08909369
- Volume :
- 20
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Genes & Development
- Publication Type :
- Academic Journal
- Accession number :
- 19711023
- Full Text :
- https://doi.org/10.1101/gad.1384406