A novel p53‐inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis‐inducing factor (AIF)

摘要

>The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 ( data-equation-construct="true" class="math-equation-construct"> data-equation-image="true" class="math-equation-image"> alt="math formula" src="http://onlinelibrary.wiley.com/store/10.1016/S0014-5793(02)03049-1/asset/equation/feb2s0014579302030491-math-si1.gif?v=1&s=b9163f3d6c618b638cb45549db8afaeb9ab73eee" class="inlineGraphic" /> data-equation-mathml="true" class="math-equation-mathml" style="display:none">53- data-equation-construct="true" class="math-equation-construct"> data-equation-image="true" class="math-equation-image"> alt="math formula" src="http://onlinelibrary.wiley.com/store/10.1016/S0014-5793(02)03049-1/asset/equation/feb2s0014579302030491-math-si2.gif?v=1&s=73b37c82db61882d4740b876c8a8af98aaa535d7" class="inlineGraphic" /> data-equation-mathml="true" class="math-equation-mathml" style="display:none">esponsive data-equation-construct="true" class="math-equation-construct"> data-equation-image="true" class="math-equation-image"> alt="math formula" src="http://onlinelibrary.wiley.com/store/10.1016/S0014-5793(02)03049-1/asset/equation/feb2s0014579302030491-math-si3.gif?v=1&s=a91b0e5960d1aede687874f10d4ee42abd07f50e" class="inlineGraphic" /> data-equation-mathml="true" class="math-equation-mathml" style="display:none">ene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3–q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.