junB promoter regulation: Ras mediated transactivation by c-Ets-1 and c-Ets-2.
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).
Coffer
P
P
Hubrecht Laboratorium, Utrecht, The Netherlands.
de Jonge
M
M
Mettouchi
A
A
Binetruy
B
B
Ghysdael
J
J
Kruijer
W
W
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D011905:Genes, ras; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D017384:Sequence Deletion; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494070:Ets2 protein, mouse; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases