Document Detail

BLIMP1 regulates cell growth through repression of p53 transcription.
MedLine Citation:
PMID:  17264218     Owner:  NLM     Status:  MEDLINE    
Tight regulation of p53 is essential for maintaining normal cell growth. Here we report that BLIMP1 acts in an autoregulatory feedback loop that controls p53 activity through repression of p53 transcription. p53 binds to and positively regulates BLIMP1, which encodes for a known B cell transcriptional repressor. Knockdown of BLIMP1 by siRNA results in both apoptosis and growth arrest in human colon cancer cells and cell-cycle arrest in primary human fibroblasts. Interestingly, the levels of both p53 mRNA and protein are substantially increased after BLIMP1 depletion, which is accompanied by the induction of p53 target genes. Importantly, the apoptosis induced by BLIMP1 depletion in HCT116 cells is largely abrogated in cells lacking p53 or in cells depleted in p53 by siRNA. We further demonstrate that BLIMP1 binds to the p53 promoter and represses p53 transcription, and this provides a mechanistic explanation for the induction of p53 response in cells depleted of BLIMP1. Hence, suppression of p53 transcription is a crucial function of endogenous BLIMP1 and is essential for normal cell growth.
Junli Yan; Jianming Jiang; Ching Aeng Lim; Qiang Wu; Huck-Hui Ng; Keh-Chuang Chin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-30
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 Feb 
Date Detail:
Created Date:  2007-02-07     Completed Date:  2007-03-22     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1841-6     Citation Subset:  IM    
Gene Expression Laboratory, Genome Institute of Singapore, Singapore.
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MeSH Terms
Cell Enlargement*
Cell Line
Cell Survival / genetics
Gene Expression Regulation / physiology*
HCT116 Cells
Protein Binding / genetics
Repressor Proteins / metabolism,  physiology*
Transcription Factors / metabolism,  physiology*
Transcription, Genetic*
Tumor Suppressor Protein p53 / antagonists & inhibitors*,  biosynthesis,  genetics*,  metabolism
Reg. No./Substance:
0/Repressor Proteins; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 138415-26-6/PRDM1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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