Transcription factor ATF2 regulation by the JNK signal transduction pathway.
Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH2-terminal protein kinase (JNK). Activating transcription factor-2 (ATF2) was found to be a target of the JNK signal transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced threonine residues within the NH2-terminal activation domain. The replacement of these phosphorylation sites with alanine inhibited the transcriptional activity of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited ATF2 transcriptional activity. Together, these data demonstrate a role for the JNK signal transduction pathway in transcriptional responses mediated by ATF2.
Gupta
S
S
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605.
Campbell
D
D
Dérijard
B
B
Davis
R J
RJ
D051698:Activating Transcription Factor 2; D017500:Adenovirus E1A Proteins / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D016350:Leucine Zippers; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D051698:Activating Transcription Factor 2; D017500:Adenovirus E1A Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D007375:Interleukin-1; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases