Dominant-negative TAK1 induces c-Myc and G(0) exit in liver.
Transforming growth factor-beta (TGF-beta)-activated kinase 1 (TAK1), a serine/threonine kinase, is reported to function in the signaling pathways of TGF-beta, interleukin 1, and ceramide. However, the physiological role of TAK1 in vivo is largely unknown. To assess the function of TAK1 in vivo, dominant-negative TAK1 (dnTAK1) was expressed in the rat liver by adenoviral gene transfer. dnTAK1 expression abrogated c-Jun NH(2)-terminal kinase and c-Jun but not nuclear factor (NF)-kappaB or SMAD activation after partial hepatectomy (PH). Expression of dnTAK1 or TAM-67, a dominant-negative c-Jun, induced G(0) exit in quiescent liver and accelerated cell cycle progression after PH. Finally, dnTAK1 and TAM-67 induced c-myc expression in the liver before and after PH, suggesting that G(0) exit induced by dnTAK1 and TAM-67 is mediated by c-myc induction.
Bradham
C A
CA
Department of Medicine, University of North Carolina at Chapel Hill, 27707, USA.
Hatano
E
E
Brenner
D A
DA
D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D016758:Genes, jun / Q000187:drug effects / Q000502:physiology; D016259:Genes, myc / Q000187:drug effects / Q000502:physiology*; D006498:Hepatectomy / Q000379:methods; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000502:physiology*; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C493958:Cdkn1a protein, rat; C497787:Smad3 protein, rat; C490811:Smad4 protein, rat; C439528:TAM67 peptide