Regulation of the Max gene expression by different mitogenic pathways in dog primary thyrocytes.
The family of Myc proteins appears to function through heterodimerization with the bHLH-Zip protein Max. We have investigated the regulation of Max mRNA in primary cultured dog thyrocytes whose proliferation is stimulated by three distinct mitogenic pathways: (1) the thyrotropin (TSH) cascade mediated by cyclic AMP, (2) the protein kinase C pathway activated by diacylglycerol and phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (TPA), (3) a protein tyrosine kinase system activated by epidermal growth factor (EGF). Among these cascades only the first is compatible with differentiation. We have observed that the mRNA of Max is stable and regulated differentially by the three pathways in our system. TSH decreases the level of the messenger while EGF or TPA increases it with early delayed kinetics. The effect of cyclic AMP on the accumulation of Max is observed even in the presence of cycloheximide, while the EGF- or TPA-induced increase is cycloheximide sensitive, suggesting differences in regulation pathways. Max mRNA is regulated with the same intensity, but in a more delayed fashion than the messenger of c-myc. As Max protein mediates the transcriptional effects of c-Myc our results are compatible with a mediator role of Max in modulating the cell sensitivity to the proliferative signal c-Myc.
Pirson
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I
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Reuse
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Dumont
J E
JE
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004285:Dogs; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression; D016259:Genes, myc; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000494:pharmacology; D014157:Transcription Factors
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D012333:RNA, Messenger; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D013972:Thyrotropin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate