Document Detail

CRL2(LRR-1) targets a CDK inhibitor for cell cycle control in C. elegans and actin-based motility regulation in human cells.
MedLine Citation:
PMID:  21074724     Owner:  NLM     Status:  MEDLINE    
The Cip/Kip CDK inhibitor (CKI) p21(Cip1/WAF1) has a critical role in the nucleus to limit cell proliferation by inhibiting CDK-cyclin complexes. In contrast, cytoplasmic p21 regulates cell survival and the actin cytoskeleton. These divergent functions for p21 in different cellular compartments suggest the necessity for complex regulation. In this study, we identify the CRL2(LRR-1) ubiquitin ligase as a conserved regulator of Cip/Kip CKIs that promotes the degradation of C. elegans CKI-1 and human p21. The nematode CRL2(LRR-1) complex negatively regulates nuclear CKI-1 levels to ensure G1-phase cell cycle progression in germ cells. In contrast, human CRL2(LRR1) targets cytoplasmic p21, acting as a critical regulator of cell motility that promotes a nonmotile stationary cell state by preventing p21 from inhibiting the Rho/ROCK/LIMK pathway. Inactivation of human CRL2(LRR1) leads to the activation of the actin-depolymerizing protein cofilin, dramatic reorganization of the actin cytoskeleton, and increased cell motility.
Natalia G Starostina; Jennifer M Simpliciano; Michael A McGuirk; Edward T Kipreos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Developmental cell     Volume:  19     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2010-12-23     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  753-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Actins / metabolism*
Caenorhabditis elegans / cytology,  physiology*
Caenorhabditis elegans Proteins / genetics,  metabolism*
Cell Cycle / physiology*
Cell Movement / physiology*
Cell Nucleus / metabolism
Cullin Proteins / genetics,  metabolism
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism*
Cytoskeleton / metabolism
Germ Cells / cytology,  physiology
Protein Kinase Inhibitors / metabolism
Recombinant Fusion Proteins / genetics,  metabolism
Repressor Proteins / genetics,  metabolism*
Grant Support
1R01GM074212/GM/NIGMS NIH HHS; R01 GM074212/GM/NIGMS NIH HHS; R01 GM074212-03/GM/NIGMS NIH HHS; R01 GM074212-03S1/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Actins; 0/CUL2 protein, human; 0/Caenorhabditis elegans Proteins; 0/Cullin Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/LRR1 protein, human; 0/Protein Kinase Inhibitors; 0/Recombinant Fusion Proteins; 0/Repressor Proteins
Comment In:
Dev Cell. 2010 Nov 16;19(5):641-3   [PMID:  21074711 ]

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