Disease relevance of NLRP4

• Tumor regression was observed in mice bearing LC-6 lung, St-4 and St-40 stomach, Li-7 liver, PAN-2 pancreas, and MX-1 breast carcinomas [1].

High impact information on NLRP4

• Furthermore, PAN2 association with IKKalpha was demonstrated by co-immunoprecipitation assays, suggesting a direct effect on the IKK complex [2].
• PAN2 also inhibited the cytokine-mediated activation of IKKalpha and IKKbeta as measured by in vitro kinase assays [2].
• This protein thus resembles Cryopyrin, a protein implicated in hereditary hyperinflammation syndromes, and was termed PAN2 for PAAD and NACHT-containing protein 2 [2].
• This PAN2-mediated suppression of NF-kappaB was evident both in reporter gene assays that measured NF-kappaB transcriptional activity and electromobility shift assays that measured NF-kappaB DNA binding activity [2].
• Recently we had reported the isolation of the human RNH2 cDNA and its expression, which is limited to the human testis [3].

Biological context of NLRP4

• The human RNH2 is also expressed limited to testis, and then it is suggested that the human Rnh2 gene may also play critical roles in human spermatogenesis [4].
• DCP2-mediated decapping takes place after deadenylation and may serve as a backup mechanism for triggering mRNA decay when initial deadenylation by PAN2 is compromised [5].

Associations of NLRP4 with chemical compounds

• Reactions of ethenyloxirane with amino (RNH2) and thiol (R'SH) nucleophiles occur by an SN2 mechanism involving competing ring cleavage at C-2 and C-3 [6].
• In contrast, 2-ethenyl-2-methyloxirane reacts with amino (RNH2) and thiolate (R'S-) nucleophiles in methanol by regioselective SN2 attack at C-3 ("neo-pentyl" position) [6].

References