| First Author | Jetton D | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 8 | Pages | 114641 |
| PubMed ID | 39154339 | Mgi Jnum | J:353859 |
| Mgi Id | MGI:7714426 | Doi | 10.1016/j.celrep.2024.114641 |
| Citation | Jetton D, et al. (2024) Non-canonical autophosphorylation of RIPK1 drives timely pyroptosis to control Yersinia infection. Cell Rep 43(8):114641 |
| abstractText | Caspase-8-dependent pyroptosis has been shown to mediate host protection from Yersinia infection. For this mode of cell death, the kinase activity of receptor-interacting protein kinase 1 (RIPK1) is required, but the autophosphorylation sites required to drive caspase-8 activation have not been determined. Here, we show that non-canonical autophosphorylation of RIPK1 at threonine 169 (T169) is necessary for caspase-8-mediated pyroptosis. Mice with alanine in the T169 position are highly susceptible to Yersinia dissemination. Mechanistically, the delayed formation of a complex containing RIPK1, ZBP1, Fas-associated protein with death domain (FADD), and caspase-8 abrogates caspase-8 maturation in T169A mice and leads to the eventual activation of RIPK3-dependent necroptosis in vivo; however, this is insufficient to protect the host, suggesting that timely pyroptosis during early response is specifically required to control infection. These results position RIPK1 T169 phosphorylation as a driver of pyroptotic cell death critical for host defense. |
