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Puma, noxa, p53, and p63 differentially mediate stress pathway induced apoptosis

Cell Death Dis. 2021-06; 
Jun Wang, Holly R Thomas, Zhang Li, Nan Cher Florence Yeo, Hannah E Scott, Nghi Dang, Mohammed Iqbal Hossain, Shaida A Andrabi, John M Parant
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摘要

Cellular stress can lead to several human disease pathologies due to aberrant cell death. The p53 family (tp53, tp63, and tp73) and downstream transcriptional apoptotic target genes (PUMA/BBC3 and NOXA/PMAIP1) have been implicated as mediators of stress signals. To evaluate the importance of key stress response components in vivo, we have generated zebrafish null alleles in puma, noxa, p53, p63, and p73. Utilizing these genetic mutants, we have deciphered that the apoptotic response to genotoxic stress requires p53 and puma, but not p63, p73, or noxa. We also identified a delayed secondary wave of genotoxic stress-induced apoptosis that is p53/puma independent. Contrary to genotoxic stress, ER stress-induced ap... More

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