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
A.N. Kukushkin,1,2,* S.B. Svetlikova,1,2 V.A. Pospelov 1,2
1 Institute of Cytology RAS, St. Petersburg, and 2 St. Petersburg State University;
* e-mail: kan@mail.cytspb.rssi.ru
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.
Key words: MKP-1 and c-foss, anisomycin, transformed fibroblasts, E1A and cHa-ras oncogenes
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