title: c-Jun N-terminal kinase phosphorylates DCP1a to control formation of P bodies.
abstract: 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 coimmunoprecipitated 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 IκBα mRNA, whereas overexpressed DCP1a blocked IL-8 transcription and suppressed p65 NF-κB 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.
authors.affiliation: Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, 35392 Giessen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Rzeczkowski
authors.forename: Knut
authors.initials: K
authors.lastname: Beuerlein
authors.forename: Helmut
authors.initials: H
authors.lastname: Müller
authors.forename: Oliver
authors.initials: O
authors.lastname: Dittrich-Breiholz
authors.forename: Heike
authors.initials: H
authors.lastname: Schneider
authors.forename: Daniela
authors.initials: D
authors.lastname: Kettner-Buhrow
authors.forename: Helmut
authors.initials: H
authors.lastname: Holtmann
authors.forename: Michael
authors.initials: M
authors.lastname: Kracht
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000201:enzymology*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013312:Stress, Physiological; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D004722:Endoribonucleases; D005095:Exoribonucleases; D051550:I-kappa B Kinase; D018836:Inflammation Mediators; D007375:Interleukin-1; D016209:Interleukin-8; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D008869:Microtubule-Associated Proteins; D011506:Proteins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051996:Transcription Factor RelA; D000099151:MAP Kinase Kinase Kinase 7; C508606:CXCL8 protein, human; C507914:EDC4 protein, human; C498143:RELA protein, human; C496559:CHUK protein, human; C466280:smad4-interacting protein SMIF, mouse; C470512:XRN1 protein, human; C466279:DCP1A protein, human