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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2009-8-6
pubmed:abstractText
Cofilin, a ubiquitously expressed actin binding protein, is responsible for the formation of the actin cytoskeleton and is indispensable for cell cycle control. However, the association between cofilin expression and the cell cycle remains to be elucidated. In this study, we found that the expression level of cofilin upregulated in G(1) phase-arrested confluent cells, while knockdown of cofilin expression by small interference RNA (siRNA) in these cells led to a reduction in the population of G(1) cells. To investigate the role of cofilin in the control of G(1) phase progression, a tet-on gene expression system was introduced to overexpress different concentrations of cofilin in cells. The results showed that G(1) phase progression was blocked following induction of exogenous cofilin. A survey of the cell cycle proteins controlling the G(1) phase progression revealed that the cyclin-dependent kinase inhibitor (CKI) p27(kip1) was the primary molecule induced by overexpressed cofilin in a time and dose dependent manner. Upregulated p27(kip1) repressed phosphorylation of the retinoblastoma protein (Rb) mediated by cyclin D1/CDK4 activity. Conversely, siRNA against p27(kip1) expression in the cofilin overexpressing cells released the G(1) phase arrest. Furthermore, we found that overexpression of cofilin led to induction of p27(kip1) gene promoter transactivation using luciferase reporter gene assay. This effect was associated with increase of p27(kip1) mRNA transiently. In addition, inhibition of threonine-187 phosphorylation of p27(kip1) protein for ubiquitinyl-proteasomal mediated degradation was also involved in upregulation of p27(kip1). These data suggest that cofilin expression and its regulation of p27(kip1) expression is important for the control of G(1) phase progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2365-74
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Regulated expression of cofilin and the consequent regulation of p27(kip1) are essential for G(1) phase progression.
pubmed:affiliation
Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't