Document Detail


Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation.
MedLine Citation:
PMID:  15526030     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Axin and p53 are tumor suppressors, controlling cell growth, apoptosis, and development. We show that Axin interacts with homeodomain-interacting protein kinase-2 (HIPK2), which is linked to UV-induced p53-dependent apoptosis by interacting with, and phosphorylating Ser 46 of, p53. In addition to association with p53 via HIPK2, Axin contains a separate domain that directly interacts with p53 at their physiological concentrations. Axin stimulates p53-dependent reporter transcription in 293 cells, but not in 293T, H1299, or SaOS-2 cells that are defective in p53 signaling. Axin, but not AxindeltaHIPK2, activates HIPK2-mediated p53 phosphorylation at Ser 46, facilitating p53-dependent transcriptional activity and apoptosis. Specific knockdown of Axin by siRNA reduced UV-induced Ser-46 phosphorylation and apoptosis. Kinase-dead HIPK2 reduced Axin-induced p53-dependent transcriptional activity, indicating that Axin stimulates p53 function through HIPK2 kinase activity. Interestingly, HIPK2deltaAxin that lacks its Axin-binding region acts as a dominant-positive form in p53 activation, suggesting that the Axin-binding region of HIPK2 is a putative autoinhibitory domain. These results show that Axin acts as a tumor suppressor by facilitating p53 function through integration of multiple factors.
Authors:
Yanning Rui; Zhen Xu; Shuyong Lin; Qinxi Li; Hongliang Rui; Wen Luo; Hai-Meng Zhou; Po-Yan Cheung; Zhenguo Wu; Zhiyun Ye; Peng Li; Jiahuai Han; Sheng-Cai Lin
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-11-04
Journal Detail:
Title:  The EMBO journal     Volume:  23     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-24     Completed Date:  2005-06-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  4583-94     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology*,  radiation effects
Carrier Proteins / genetics,  metabolism*
Cell Line, Tumor
Enzyme Activation
Genes, Reporter
Humans
Mutation
Phosphorylation
Protein Binding
Protein-Serine-Threonine Kinases / genetics,  metabolism*
RNA, Small Interfering / pharmacology
Repressor Proteins / genetics,  metabolism,  physiology*
Serine / metabolism
Transcription, Genetic
Tumor Suppressor Protein p53 / metabolism,  physiology*
Ultraviolet Rays
Chemical
Reg. No./Substance:
0/Axin protein; 0/Carrier Proteins; 0/RNA, Small Interfering; 0/Repressor Proteins; 0/Tumor Suppressor Protein p53; 56-45-1/Serine; EC 2.7.1.-/HIPK2 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

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