It has been reported that IPAF/NLRC4, ASC, and caspase-1 are transcriptional targets

of p53 [28, 29]. One point of convergence might be the inflammasome adaptor ASC, which has been shown to play an essential role in the intrinsic mitochondrial pathway of apoptosis through a p53-Bax network [30]. ASC can co-localize and interact with Bax at mitochondria [30]. Bax is a pro-apoptotic protein that causes mitochondrial dysfunction, including release of cytochrome c during apoptosis. It is possible that ASC activity is suppressed in Nlrp3−/− cells, thus conferring a survival advantage by allowing cells to escape pyroptosis. However, it remains to be determined whether NLRP3 interacts directly or indirectly with p53 or other DDR mediators either in the cytosol or at mitochondrial

sites, and whether any link exists between these two pathways Quizartinib chemical structure in controlling cell survival and inflammatory responses. A more detailed understanding of the molecular interactions involving NLRP3 and its partners at mitochondria may provide opportunities to I-BET-762 molecular weight better understand these apoptotic effects. There is, however, evidence to suggest that inflammasomes can be directly involved in suppression of the DNA repair machinery. Recent data supported the idea that activation of NLRP3 and IPAF/NLRC4 inflammasomes could be directly involved in caspase-1 block of DNA repair. It was shown Ureohydrolase that inflammasome-mediated activation of caspase-1 triggers caspase-7 cleavage, which in turns mediates proteolytic deactivation of poly(ADP-ribose) polymerase 1, a DNA damage repair enzyme [31, 32]. Poly-ADP-ribosylation mediated by PARP-1 causes chromatin decondensation around damage sites, recruitment of repair machinery, and accelerates DNA damage repair. These observations suggest that the NLRP3 inflammasome, by inactivating

poly(ADP-ribose) polymerase 1, may play a more direct role in DNA repair suppression. The finding that the NLRP3 inflammasome controls DDR as well as the processing of pro-IL-1β and pro-IL-18 into mature cytokines prompts us to speculate that NLRP3 may also be involved in tumor surveillance. There is extensive evidence that chronic inflammation promotes cancer, and thus it was initially hypothesized that the NLRP3 inflammasome might favor tumorigenesis. Several groups have recently examined the role of NLRP3 in inducible models of colitis-induced cancer, but so far these investigations have yielded conflicting results. In some studies, the NLRP3 inflammasome seemed to enhance colitis-associated cancer, whereas in others this molecule was reported to have a protective role in tumor progression [33-38].