Document Detail


Cell cycle-independent upregulation of p27Kip1 by p21Waf1 in K562 cells.
MedLine Citation:
PMID:  11641776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cellular differentiation frequently involves sequential peaks in the expression of cyclin-dependent kinase inhibitors (cdki's). For example, an increase in levels of the cdki p27Kip1 follows upregulation of p21Waf1 in several cell types induced to differentiate by diverse stimuli. In this study, we have investigated whether p21Waf1 expression itself, rather than the differentiating agent, could be increasing p27Kip1 protein levels. We used an inducible p21Waf1 expression vector in a K562 leukemic cell model which we had previously shown to initiate differentiation following p21Waf1 upregulation. The current study reports that p21Waf1 upregulated p27Kip1 protein without altering p27Kip1 mRNA levels. This effect did not depend on G1-phase arrest-the increase in p27Kip1 occurred at all phases of the cell cycle. p21Waf1-expressing extracts inhibited phosphorylation of p27Kip1 on threonine-187, leading to decreased ubiquitination and decreased proteasomal destruction of p27Kip1. In K562 cells, upregulation of p27Kip1 by p21Waf1 during differentiation facilitated an ordered transition between these two cdki's, each of which may distinctly influence the differentiation process.
Authors:
R A Steinman; Y Lu; B Yaroslavskiy; C Stehle
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  20     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-19     Completed Date:  2001-11-01     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  6524-30     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Steinman@imap.pitt.edu
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MeSH Terms
Descriptor/Qualifier:
CDC2-CDC28 Kinases*
Cell Cycle
Cell Cycle Proteins / metabolism*
Cell Differentiation
Cell Extracts
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases / metabolism
Cyclins / genetics,  physiology*
Humans
K562 Cells
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins*
Transfection
Tumor Suppressor Proteins*
Up-Regulation
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cell Extracts; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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