| First Author | Li D | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34029184 | Mgi Jnum | J:307062 |
| Mgi Id | MGI:6712108 | Doi | 10.7554/eLife.67409 |
| Citation | Li D, et al. (2021) A phosphorylation of RIPK3 kinase initiates an intracellular apoptotic pathway that promotes prostaglandin2alpha-induced corpus luteum regression. Elife 10:e67409 |
| abstractText | Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) normally signals to necroptosis by phosphorylating MLKL. We report here that when the cellular RIPK3 chaperone Hsp90/CDC37 level is low, RIPK3 also signals to apoptosis. The apoptotic function of RIPK3 requires phosphorylation of the serine 165/threonine 166 sites on its kinase activation loop, resulting in inactivation of RIPK3 kinase activity while gaining the ability to recruit RIPK1, FADD, and caspase-8 to form a cytosolic caspase-activating complex, thereby triggering apoptosis. We found that PGF2alpha induces RIPK3 expression in luteal granulosa cells in the ovary to cause luteal regression through this RIPK3-mediated apoptosis pathway. Mice carrying homozygous phosphorylation-resistant RIPK3 S165A/T166A knockin mutations failed to respond to PGF2alpha but retained pro-necroptotic function, whereas mice with phospho-mimicking S165D/T166E homozygous knock-in mutation underwent spontaneous apoptosis in multiple RIPK3-expressing tissues and died shortly after birth. Thus, RIPK3 signals to either necroptosis or apoptosis depending on its serine 165/threonine 166 phosphorylation status. |
