Document Detail


Evidence for cytosolic p27(Kip1) ubiquitylation and degradation during adipocyte hyperplasia.
MedLine Citation:
PMID:  17189539     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Subcellular localization has been shown to play an important role in determining activity and accumulation of p27 protein during cell cycle progression. The purpose of this study was to examine p27 localization and ubiquitylation in relation to E3 ligase expression during adipocyte hyperplasia. RESEARCH METHODS AND PROCEDURES: This study used the murine 3T3-L1 preadipocyte model to examine p27 regulation during synchronous cell cycle progression. Cell lysates were isolated over time after hormonal stimulation, fractionated to cytosolic and nuclear compartments, and immunoblotted for relative protein determinations. RESULTS: Data presented in this study show that p27 was present in the cytosol and nucleus in density-arrested preadipocytes and that abundance in both compartments decreased in a phase-specific manner as preadipocytes synchronously re-entered the cell cycle during early phases of adipocyte differentiation. Blocking CRM1-mediated nuclear export did not prevent degradation, nor did it cause nuclear accumulation of p27, suggesting that distinct mechanisms mediating cytosolic and nuclear p27 degradation were involved. Treating preadipocytes with a potent and specific proteasome inhibitor during hormonal stimulation prevented Skp2 accumulation and p27(187) phosphorylation, which are essential events for SCF(Skp2) E3 ligase activity and nuclear p27 ubiquitylation during S/G(2) phase progression. Proteasome blockade also resulted in the first evidence of cytosolic p27 ubiquitylation during late G(1) phase as preadipocytes undergo the transition from quiescence to proliferation. DISCUSSION: These data are consistent with the postulate that p27 is ubiquitylated and targeted for degradation by the 26S proteasome in a phase-specific manner by distinct ubiquitin E3 ligases localized to the cytosol and nucleus during adipocyte hyperplasia.
Authors:
Corinth A Auld; Ron F Morrison
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Obesity (Silver Spring, Md.)     Volume:  14     ISSN:  1930-7381     ISO Abbreviation:  Obesity (Silver Spring)     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-25     Completed Date:  2007-02-20     Revised Date:  2008-01-21    
Medline Journal Info:
Nlm Unique ID:  101264860     Medline TA:  Obesity (Silver Spring)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2136-44     Citation Subset:  IM    
Affiliation:
Department of Nutrition, 318 Stone Building, UNC Greensboro, Greensboro, NC 27402, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / metabolism*
Animals
Cell Cycle Proteins / metabolism*
Cell Differentiation
Cell Fractionation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27 / pharmacology
G1 Phase
G2 Phase
Intracellular Signaling Peptides and Proteins / metabolism*
Mice
Proteasome Endopeptidase Complex / metabolism*
Protein Kinase Inhibitors / pharmacology
S Phase
Ubiquitin / metabolism
Grant Support
ID/Acronym/Agency:
1R21DK072067-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1B protein, human; 0/Cell Cycle Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Protein Kinase Inhibitors; 0/Ubiquitin; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 3.4.25.1/Proteasome Endopeptidase Complex

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


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