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bioRxiv · 10.1101/2020.08.17.254318

Casein Kinase 1G2 Suppresses Necroptosis-Promoted Testis Aging by Inhibiting Receptor-Interacting Kinase 3

Wang, X.·Li, D.·Ai, Y.·Guo, J.·Dong, B.·Li, L.·Cai, G.·Chen, S.·Xu, D.·Wang, F.
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Abstract

Casein kinases are a large family of intracellular serine/threonine kinases that control a variety of cellular signaling functions. Here we report that a member of casein kinase 1 family, casein kinase 1G2, CSNK1G2, binds and inhibits the activation of receptor-interacting kinase 3, RIP3, thereby attenuating RIP3-mediated necroptosis. The binding of CSNK1G2 to RIP3 is triggered by auto-phosphorylation at serine 211/threonine 215 sites in its C-terminal domain. CSNK1G2-knockout mice showed significantly enhanced necroptosis response and pre-maturing aging of their testis, a phenotype that was rescued by either double knockout of the RIP3 gene or feeding the animal with a RIP1 kinase inhibitor-containing diet. Moreover, CSNK1G2 is also co-expressed with RIP3 in human testis, and the necroptosis activation marker phospho-MLKL was observed in the testis of old (>80) but not young men, indicating that the testis-aging program carried out by the RIP3-mediated and CSNK1G2-attenuated necroptosis is evolutionarily conserved between mice and men.

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Wang, X., Li, D., Ai, Y., Guo, J., Dong, B., Li, L., Cai, G., Chen, S., Xu, D., Wang, F.. 2020-08-18. Casein Kinase 1G2 Suppresses Necroptosis-Promoted Testis Aging by Inhibiting Receptor-Interacting Kinase 3. https://doi.org/10.1101/2020.08.17.254318

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