BLIMP1 regulates cell growth through repression of p53 transcription.
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.
Yan
Junli
J
Gene Expression Laboratory, Genome Institute of Singapore, Singapore.
Jiang
Jianming
J
Lim
Ching Aeng
CA
Wu
Qiang
Q
Ng
Huck-Hui
HH
Chin
Keh-Chuang
KC
D049108:Cell Enlargement; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1