Deregulated repression of c-Jun provides a potential link to its role in tumorigenesis

Cell Cycle. 2004 Feb;3(2):111-3.

Abstract

The transcription factor c-Jun cooperates with oncogenic alleles of ras in malignant transformation. Constitutively active Ras causes, via activation of mitogen activated protein kinases, phosphorylation of c-Jun which is essential for subsequent target gene activation and tumorigenesis. Studying the mechanisms controlling c-Jun activity we found that its transcription activation function is actively repressed by a presumably multimeric repressor complex that includes histone deacetylase 3 as a critical subunit. Suppression of c-Jun is relieved by MAP kinase-mediated phosphorylation and/or titration of inhibitor components. The viral tumorigenic counterpart of c-Jun, v-Jun, escapes this inhibition, suggesting deregulated transcriptional activity of c-Jun as a relevant cause for carcinogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Transformation, Neoplastic / metabolism*
  • Enzyme Activation / physiology
  • Genes, jun / physiology*
  • Histone Deacetylases / metabolism
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Phosphorylation
  • Repressor Proteins / metabolism*
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology
  • ras Proteins / metabolism

Substances

  • Repressor Proteins
  • Mitogen-Activated Protein Kinase Kinases
  • Histone Deacetylases
  • histone deacetylase 3
  • ras Proteins