HCK regulates NLRP12-mediated PANoptosis

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(21)

Опубликована: Май 23, 2025

NOD-like receptors (NLRs) are a highly conserved family of cytosolic pattern recognition that drive innate immune responses against pathogens, pathogen-associated molecular patterns, damage-associated and homeostatic disruptions. Within the NLR family, NLRP12 was recently identified as key regulator PANoptosis, which is an immune, lytic cell death pathway initiated by sensors driven caspases RIPKs through PANoptosome complexes. While activation critical for maintaining homeostasis, aberrant has been implicated in broad range disorders, including cancers metabolic, infectious, autoinflammatory, hemolytic diseases. However, mechanisms remain poorly understood. Here, we hematopoietic kinase (HCK) NLRP12-mediated PANoptosis. HCK expression significantly upregulated response to NLRP12-PANoptosome triggers. Moreover, Hck knockdown inhibited Computational analyses residues putative interaction interface between HCK, suggesting likely binds region its NACHT domain pyrin (PYD); removal PYD abrogated this vitro. Overall, our work identifies it may serve potential therapeutic target mitigating inflammation pathology.

Язык: Английский

ExSPECKt the unexpected: NLRP3-caspase-8-dependent cell death in RBCs

Cell, Год журнала: 2025, Номер 188(11), С. 2833 - 2835

Опубликована: Май 1, 2025

Язык: Английский