c-Jun N-terminal kinase phosphorylates DCP1a to control formation of P bodies

Cytokines and stress-inducing stimuli signal through c-Jun N-terminal kinase (JNK) using a diverse and only partially defined set of downstream effectors. In this paper, the decapping complex subunit DCP1a was identified as a novel JNK target. JNK phosphorylated DCP1a at residue S315 in vivo and in vitro and co-immunoprecipitated and colocalized with DCP1a in processing bodies (P bodies). Sustained JNK activation by several different inducers led to DCP1a dispersion from P bodies, whereas IL-1 treatment transiently increased P body number. Inhibition of TAK1-JNK signaling also affected the number and size of P bodies and the localization of DCP1a, Xrn1, and Edc4. Transcriptome analysis further identified a central role for DCP1a in IL-1-induced messenger ribonucleic acid (mRNA) expression. Phosphomimetic mutation of S315 stabilized IL-8 but not I. B. mRNA, whereas overexpressed DCP1a blocked IL-8 transcription and suppressed p65 NF-kappa B nuclear activity. Collectively, these data reveal DCP1a as a multifunctional regulator of mRNA expression and suggest a novel mechanism controlling the subcellular localization of DCP1a in response to stress or inflammatory stimuli.