title: Activation of JNK/SAPK pathway is not directly inhibitory for cell cycle progression in NIH3T3 cells.
abstract: In this study the induction of stress activated protein kinase (SAPK) activity by protein synthesis inhibitors was shown not to inhibit cellular proliferation. Anisomycin induced strong SAPK activity at non-inhibitory concentrations for either protein or DNA synthesis, while the other two inhibitors, emetine and cycloheximide, blocked cell cycle progression without strong SAPK induction. With all three inhibitors, the induction of SAPK activity was always accompanied by protein synthesis inhibition to some extent. Stimulation of mRNA expression of the genes c-jun, c-fos and c-myc correlated well with SAPK induction, but not with cell cycle inhibition. With concentrations of each inhibitor able to block DNA synthesis, no induction of message for the cyclin dependent kinase inhibitor waf-1 was observed; while induction of gadd45 message indicated that the cells might be responding to growth-arrest or DNA damage. The inability of microinjected E2F/DP1 transcription factor proteins to overcome the inhibition of DNA synthesis induced by protein synthesis inhibitors indicate that blockage of an early event in cell cycle progression had occurred. These results indicate that the SAPK induction by protein synthesis inhibitors has no proliferative consequences.
authors.affiliation: The Cleveland Clinic Foundation Research Institute, Department of Molecular Biology, Ohio 44195, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shu
authors.forename: M
authors.initials: M
authors.lastname: Hitomi
authors.forename: D
authors.initials: D
authors.lastname: Stacey
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004640:Emetine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D011494:Protein Kinases / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000494:pharmacology; D000097642:GADD45 Proteins
chemical_list: D000841:Anisomycin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003513:Cycloheximide; D004247:DNA; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004640:Emetine; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D011494:Protein Kinases; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D000097642:GADD45 Proteins; C533431:Arid4a protein, mouse; C493736:Tfdp1 protein, mouse