Early growth response-1-dependent apoptosis is mediated by p53.
The early growth response-1 (EGR-1) protein is an anti-proliferative signal for certain tumor cells and is required for apoptosis induced by stimuli that elevate intracellular Ca2+. We present evidence that EGR-1 transactivates the promoter of the p53 gene and up-regulates p53 RNA and protein levels. Inhibition of p53 function with dominant-negative p53 mutants abrogates EGR-1-dependent apoptosis. These findings establish a direct functional link between EGR-1 and the p53-mediated cell death pathway and suggest that mutant forms of p53 in tumor cells may provide resistance to the anti-proliferative effects of EGR-1.
Nair
P
P
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA.
Muthukkumar
S
S
Sells
S F
SF
Han
S S
SS
Sukhatme
V P
VP
Rangnekar
V M
VM
D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D051766:Early Growth Response Protein 1; D006801:Humans; D017874:Immediate-Early Proteins; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012313:RNA; D019284:Thapsigargin; D004247:DNA