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J. Biol. Chem., Vol. 276, Issue 36, 33319-33327, September 7, 2001
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From the Transcriptional elongation of many eukaryotic,
prokaryotic, and viral genes is tightly controlled, which contributes
to gene regulation. Here we describe this phenomenon for the MAP
kinase phosphatase 1 (MKP-1) immediate early gene. In rat GH4C1
pituitary cells, MKP-1 mRNA is rapidly and transiently induced by
the thyrotropin-releasing hormone (TRH) and the epidermal growth factor
EGF via transcriptional activation of the gene. Ca2+
signals are necessary for the induction of MKP-1 in response to TRH but
not to EGF. Reporter gene analysis with the newly cloned rat promoter
sequence shows only limited induction in response to various stimuli,
including TRH or EGF. By nuclear run-on assays we demonstrate that in
basal conditions, a strong block to elongation in the first exon
regulates the MKP-1 gene and that stimulation with either TRH or EGF
overcomes the block. Ca2+ signals are important to release
the MKP-1 elongation block in a manner similar to the c-fos
oncogene. These results suggest that a common mechanism of intragenic
regulation may be conserved between MKP-1 and c-fos in
mammalian cells.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF357203.
MAP Kinase Phosphatase-1 Gene Transcription in Rat Neuroendocrine
Cells Is Modulated by a Calcium-sensitive Block to Elongation in the
First Exon*
,
,
,
§,
¶, and
Fondation pour Recherche Médicales,
University of Geneva, Geneva GE 1211, Switzerland
*
This work was supported by the Swiss National Science
Foundation Grants 3200-050879.97/1 and 32-61833.00 and by the Fondation pour Recherches Médicales.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Fondation pour
Recherche Médicales, 64 av. de la Roseraie, University of Geneva, 1211 Geneva, Switzerland. Tel.: 41-22-3823811; Fax: 41-22-3475979; E-mail: werner.schlegel@medecine.unige.ch.
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