Document Detail


p53 targets identified by protein expression profiling.
MedLine Citation:
PMID:  17372198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p53 triggers cell cycle arrest and apoptosis through transcriptional regulation of specific target genes. We have investigated the effect of p53 activation on the proteome using 2D gel electrophoresis analysis of mitomycin C-treated HCT116 colon carcinoma cells carrying wild-type p53. Approximately 5,800 protein spots were separated in overlapping narrow-pH-range gel strips, and 115 protein spots showed significant expression changes upon p53 activation. The identity of 55 protein spots was obtained by mass spectrometry. The majority of the identified proteins have no previous connection to p53. The proteins fall into different functional categories, such as mRNA processing, translation, redox regulation, and apoptosis, consistent with the idea that p53 regulates multiple cellular pathways. p53-dependent regulation of five of the up-regulated proteins, eIF5A, hnRNP C1/C2, hnRNP K, lamin A/C, and Nm23-H1, and two of the down-regulated proteins, Prx II and TrpRS, was examined in further detail. Analysis of mRNA expression levels demonstrated both transcription-dependent and transcription-independent regulation among the identified targets. Thus, this study reveals protein targets of p53 and highlights the role of transcription-independent effects for the p53-induced biological response.
Authors:
Rubaiyat Rahman-Roblick; Uwe Johannes Roblick; Ulf Hellman; Paolo Conrotto; Tao Liu; Susanne Becker; Daniel Hirschberg; Hans Jörnvall; Gert Auer; Klas G Wiman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-19
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-28     Completed Date:  2007-05-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5401-6     Citation Subset:  IM    
Affiliation:
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Cell Line, Tumor
Colonic Neoplasms / metabolism
Electrophoresis, Gel, Two-Dimensional
Gene Expression Profiling*
Humans
Hydrogen-Ion Concentration
Mass Spectrometry
Mitomycin / pharmacology
Neoplasm Metastasis
Neoplasms / metabolism
Oxidation-Reduction
Promoter Regions, Genetic
Proteomics / methods
Tumor Suppressor Protein p53 / biosynthesis*,  chemistry
Chemical
Reg. No./Substance:
0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 50-07-7/Mitomycin
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