Back to Search
Start Over
A phosphorylation of RIPK3 kinase initiates an intracellular apoptotic pathway that promotes prostaglandin2ainduced corpus luteum regression.
- Source :
-
eLife . 5/24/2021, p1-29. 29p. - Publication Year :
- 2021
-
Abstract
- 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 PGF2a 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 PGF2a 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2050084X
- Database :
- Academic Search Index
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- 152085510
- Full Text :
- https://doi.org/10.7554/eLife.67409