Document Detail


IKKalpha regulates the mitotic phase of the cell cycle by modulating Aurora A phosphorylation.
MedLine Citation:
PMID:  17102620     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The IKK complex includes two catalytic components, IKKalpha and IKKbeta, in addition to the scaffold protein IKKgamma/NEMO. Even though IKKalpha and IKKbeta share significant sequence homology, they have distinct biological roles with IKKbeta regulates the classical pathway of NF-kappaB activation and IKKalpha regulates the alternative pathways. In addition, it has been shown that the IKKs regulate the proliferation of both normal and tumor cells; however, the mechanisms by which the IKKs regulate the cell cycle remain to be further defined. Here, we demonstrate that IKKalpha, but not IKKbeta, has role in regulating the M phase of the cell cycle. IKKalpha siRNA knock -down resulted in increased numbers of cells in the G(2)/M phase of the cell cycle as compared to control and IKKbeta siRNA transfected HeLa cells. This effect was associated with upregulation of cyclin B1 and Plk1 protein levels and increased histone H3 phosphorylation, consistent with a potential role of IKKalpha in the regulation of M phase regulatory factors. IKKalpha was found to be associated with Aurora A in the centrosome and regulate Aurora A phosphorylation at threonine residue 288, a site which is important in modulating its kinase activity. Taken together, these data provide the evidence that IKKalpha regulates the M phase of the cell cycle by modulating Aurora A phosphorylation and activation leading to the regulation of the M phase of the cell cycle.
Authors:
ShaShi Prajapati; Zheng Tu; Yumi Yamamoto; Richard B Gaynor
Publication Detail:
Type:  Journal Article     Date:  2006-10-16
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  5     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2007-01-03     Revised Date:  2011-07-11    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2371-80     Citation Subset:  IM    
Affiliation:
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Cell Cycle
Centrosome / chemistry
Hela Cells
Humans
I-kappa B Kinase / genetics,  metabolism,  physiology*
Mitosis*
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism*
RNA, Small Interfering / pharmacology
Transfection
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/aurora kinase; EC 2.7.11.10/I-kappa B Kinase

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