Restraint of inflammasome-driven cytokine responses through the mRNA stability protein TTP.

ABSTRACT: Activation of the NLRP3 inflammasome causes extensive disturbance of cellular homeostasis, with Golgi disruption, mitochondrial dysfunction, and changes in intracellular ion concentration occurring rapidly upon stimulation. Given this, it would seem near certain that these changes might also globally affect cellular signaling pathways, yet few, if any, studies have explored this possibility. Here, we combine genomics and phosphoproteomics to identify inhibition of the ERK1/2 MAP kinase signaling cascade upon inflammasome stimulation. This loss of ERK1/2 activity results in rapid inactivation of the mRNA decay-promoting protein tristetraprolin (TTP), with loss of TTP promoting subsequent increased release of cytokines upon pyroptosis. Further, we observe significantly increased levels of TT

SUBMITTER: O'Keefe ME 

PROVIDER: S-EPMC12022669 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature