Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon (IFN)-gamma increases the sensitivity of tumor cell lines, many of which are p53 mutants, to tumor necrosis factor-alpha-mediated and anti-Fas antibody-mediated cell death. To better understand the mechanism of IFN-gamma action in modulating the cell death response independently of p53 function, we analyzed the death of the human colon adenocarcinoma cell line, HT-29, following treatment with IFN-gamma and various cytotoxic agents. Here we show that IFN-gamma modulates cell death by sensitizing the cells to killing by numerous pro-apoptotic stimuli but not pro-necrotic stimuli. Furthermore, we show that select genes from several important apoptosis-related gene families are induced by IFN-gamma, including the apoptosis-signaling receptors CD95 (Fas/APO-1) and TNFR 1 and interleukin-1beta-converting enzyme (Ice) family members Ice, CPP32 (Yama, apopain), ICErel-II (TX, Ich-2), Mch-3 (ICE-LAP3, CMH-1), Mch-4, and Mch-5 (MACH, FLICE). Of the bcl-2 family members, IFN-gamma directly induced bak but notably not bax, which is activated by p53. The IFN-responsive transcriptional activator interferon regulatory factor-1 was also strongly induced and translocated into the nucleus following IFN-gamma treatment. We propose that IFN-gamma modulates a p53-independent apoptotic pathway by both directly and indirectly inducing select apoptosis-related genes.
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PMID:Interferon-gamma modulates a p53-independent apoptotic pathway and apoptosis-related gene expression. 919 41

The non-canonical inflammasome mediates pyroptotic cell death in response to bacterial lipopolysaccharide (LPS) found in the cytosol. Understanding the mechanism and regulation of this system is of great interest, given its central role in mouse models of bacterial septic shock. In this issue of EMBO Reports, Benaoudia and colleagues sought to discover extra players in the human non-canonical inflammasome using a CRISPR library screen; the only strongly positive hit apart from the known components caspase-4 and gasdermin D was interferon regulatory factor-2 (IRF2) [1 ]. IRF2 was found to be a transcriptional activator of caspase-4, and in its absence, induction of IRF1 could substitute to maintain caspase-4 expression.
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PMID:IRF1 and IRF2 regulate the non-canonical inflammasome. 3135 1