junB promoter regulation: Ras mediated transactivation by c-Ets-1 and c-Ets-2

Oncogene. 1994 Mar;9(3):911-21.

Abstract

The Jun gene family encode components of the AP-1 transcription factor complex that regulate a variety of TRE-containing target promoters. Expression of family members is induced by a wide variety of extracellular stimuli and thought to be important in mediating cellular proliferation and differentiation. We have localized cis-acting DNA sequences in the murine junB promoter capable of mediating transcriptional activation by the proto-oncogene products c-Ets-1 and c-Ets-2. We show by promoter deletion analysis that multiple elements located between -848 and -574, and between -196 and -91 can mediate transactivation by ETS-family members in different cell types. In vitro DNA binding assays indicate that the elements identified can specifically interact with c-Ets-1 protein. Furthermore, we show that ETS-transactivation of a variety of reporter constructs is dramatically enhanced by introduction of oncogenic Ha-ras. The activation of Ras by extracellular stimuli invokes a phosphorylation cascade that includes the downstream mitogen-activated protein (MAP) kinase p44ERK-1. We further show that addition of activated p44ERK-1 MAP kinase can also enhance ETS-transactivation of junB promoter reporter constructs. Here we propose that ETS-family members play a role in the activation of junB transcription by a Ras-stimulated signal transducing pathway that includes MAP kinase(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • DNA
  • DNA-Binding Proteins*
  • Gene Expression Regulation
  • Genes, ras*
  • Mice
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Proto-Oncogene Mas
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-jun / genetics*
  • Proto-Oncogene Proteins c-jun / metabolism
  • Repressor Proteins*
  • Sequence Deletion
  • Signal Transduction
  • Trans-Activators*
  • Transcription Factors*
  • Transcriptional Activation*

Substances

  • DNA-Binding Proteins
  • ERF protein, human
  • Ets2 protein, mouse
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-jun
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • DNA
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases