Activation of JNK/SAPK pathway is not directly inhibitory for cell cycle progression in NIH3T3 cells

Oncogene. 1996 Dec 5;13(11):2421-30.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Anisomycin / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carrier Proteins*
  • Cell Cycle / drug effects*
  • Cell Cycle / genetics
  • Cell Cycle Proteins / metabolism
  • Cycloheximide / pharmacology
  • DNA / biosynthesis
  • DNA / drug effects*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • Emetine / pharmacology
  • Enzyme Activation / drug effects
  • Intracellular Signaling Peptides and Proteins
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases*
  • Protein Kinases / metabolism*
  • Protein Synthesis Inhibitors / pharmacology*
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / metabolism*
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / pharmacology

Substances

  • Arid4a protein, mouse
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins
  • Protein Synthesis Inhibitors
  • Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Retinoblastoma-Binding Protein 1
  • Tfdp1 protein, mouse
  • Transcription Factor DP1
  • Transcription Factors
  • Anisomycin
  • DNA
  • Cycloheximide
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Emetine