Novel Ser74 of NF-κB/IκBα phosphorylated by MAPK/ERK regulates temperature adaptation in oysters.

Phosphorylation of Ser32 and Ser36 controls the degradation of IκBα is the conserved cascade mechanisms of immune core signaling pathway, NF-κB pathway in metazoans, but it's response to abiotic stress and the presence of novel phosphorylation mechanisms in other species remain unclear. Herein, we reported a novel heat-induced phosphorylation site (Ser74) at oysters' major IκBα, which independently regulated ubiquitination-proteasome degradation without the requirement of phosphorylation at S32 and S36. And this site was phosphorylated by ERK/MAPK pathway, which then promoted REL nuclear translocation to activate cell survival related genes to defend heat-stress. The MAPK-NF-κB cascade exhibited divergent thermal responses and adaptation patterns between two congeneric oyster species with differential habitat temperatures, indicating its involvement in shaping temperature adaptation. This study demonstrated that the existence of complex and unique phosphorylation-mediated signaling transduction mechanism in marine invertebrates, and expanded our understanding of the evolution and function of established classical pathway crosstalk mechanisms.