Induction of FOS and JUN proteins by adrenocorticotropin and phorbol ester but not by 3',5'-cyclic adenosine monophosphate derivatives.
We report the results of an extensive kinetic analysis of the effects of ACTH, cAMP derivatives (dibutyryl cAMP and 8-bromo-cAMP) and phorbol ester (phorbol-12-myristate-13-acetate) on the expression of fos and jun gene family members at the mRNA (Northern hybridization) and protein levels (immunoprecipitation and indirect immunofluorescence) in the mouse Y-1 adrenocortical cell line. FOS and JUN proteins are induced by ACTH independently of cell cycle stage. c-Fos, fos-B, fra-1, fra-2, c-jun, and jun-B genes are induced by ACTH, the kinetic profiles for mRNAs and respective protein products being similar, except for a 1-h protein delay. Jun-D mRNA is an exception, being constitutively expressed. However, JUN D protein is induced by ACTH. phorbol-12-myristate-13-acetate closely mimics these inductive effects of ACTH. On the other hand, cAMP derivatives are not effective in inducing the fos and jun genes, except for fra-2 mRNA, JUN D protein, and to some extent JUN B protein. Clearly, ACTH is endowed with the versatile capability of modulating fos and jun gene expression, suggesting that AP-1 transcription factors play a role in ACTH mechanisms of action. ACTH receptors are likely to activate signaling routes other than the classical cAMP/protein kinase A in order to induce FOS and JUN proteins.
Kimura
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Department of Biochemistry, Institute of Chemistry, University of São Paulo, Brazil.
Sonobe
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Armelin
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Armelin
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D009363:Neoplasm Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D003609:Dactinomycin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D003513:Cycloheximide; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate