title: [Protein phosphatase MKP-1 participates in c-fos gene derepression under the action of stress factors on fibroblasts transformed with E1A and cHA-ras oncogenes].
abstract: Immediate-early response gene c-fos expression is repressed and not activated after serum stimulation of serum-starved fibroblasts transformed with E1A and cHa-ras oncogenes. We have previously shown that such stress factors as an anisomycin are able to activate c-fos gene transcription in E1A + cHa-ras transformants, wherein MEK/ERK signal pathway plays a major role in the activation. In the present paper, we investigated the role of MKP-1-dependent regulation of c-fos gene by dephosphorylation of ERK kinases. It has been shown that MKP-1 gene transcription in E1A + ras transformants is activated by anisomycin for a maximum of 1 h, and then a reduction in the level of transcription occurs. Use of inhibitors of MAP-kinase has revealed that MKP-1 gene transcription depends on MEK/ERK and JNK kinase cascades, but not om p38 cascade. The anisomycin-induced c-fos gene transcription intensified after transfection of siRNA MKP-1 into the cells. Thus, protein phosphatase MKP-1 carries a negative regulation of c-fos gene transcription by dephosphorylation of ERK kinases that are a key signal component under the action of such stress reagent as anisomycin on the E1A + ras-transformed cells.
authors.forename: A N
authors.initials: AN
authors.lastname: Kukushkin
authors.forename: S B
authors.initials: SB
authors.lastname: Svetlikova
authors.forename: V A
authors.initials: VA
authors.lastname: Pospelov
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage; D002461:Cell Line, Transformed / Q000166:cytology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D000841:Anisomycin; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat