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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yan, Junli Ng, Huck-hui Lim, Ching Aeng Jiang, Jianming Chin, Keh-chuang Wu, Qiang |
| Description | Author Affiliation: Yan J ( Gene Expression Laboratory, Genome Institute of Singapore, Singapore.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Enlargement Gene Expression Regulation Physiology Repressor Proteins Transcription Factors Transcription, Genetic Tumor Suppressor Protein P53 Antagonists & Inhibitors Genetics Cell Line Cell Survival HCT116 Cells Protein Binding Metabolism Biosynthesis Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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