Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis.
作者： J M R Lambert , A Moshfegh , P Hainaut , K G Wiman , V J N Bykov
DOI: 10.1038/ONC.2009.425
关键词: Signal transduction 、 Microarray analysis techniques 、 GADD45B 、 Mutant 、 Molecular biology 、 Tumor suppressor gene 、 Biology 、 Null cell 、 Gene expression 、 XBP1
摘要: The low molecular weight compound PRIMA-1MET reactivates mutant p53 and triggers p53-dependent apoptosis in human tumor cells. We investigated the effect of on global gene expression using microarray analysis Saos-2 cells expressing His273 parental null affected transcription a significantly larger number genes p53-expressing compared to Genes by manner include cell-cycle regulators GADD45B 14-3-3γ pro-apoptotic Noxa. Several are known target and/or contain DNA-binding motifs. also found disruption cytoskeleton, as well transcriptional activation XBP1 cleavage its mRNA, marker for endoplasmic reticulum stress. Our data show that induces through multiple transcription-dependent -independent pathways. Such integral engagement pathways leading is consistent with restoration wild-type properties likely reduce risk drug resistance development clinical applications PRIMA-1MET.
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