Long-term variations of AP-1 composition after CRH stimulation: consequence on POMC gene regulation.
It has been shown previously that the CRH-induced POMC gene transcription in the corticotroph cell line AtT-20 involves an increase in AP-1 DNA binding activity that remained elevated for at least 24 h, while induction of c-fos was transient. We showed here that there were dramatic changes in protein components of AP-1 including an initial recruitment of the transcriptional activators c-Fos and Jun-B then of Fra-2 and Jun-D. Changes in AP-1 composition were concomitant with a decrease in POMC mRNA. Moreover, the presence of Fra-2/Jun-D dimers suppressed the CRH-induction of c-fos mRNA expression as well as c-Fos/Jun-B recruitment in AP-1 complexes, suggesting the existence of autoregulatory loops of AP-1 composition that involve complex interactions between the different members of the Jun and Fos families. It is concluded that CRH stimulation of corticotroph cells involves successive recruitment of activators and repressors, possibly contributing to prevent over expression of POMC.
Becquet
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D
Interactions Fonctionnelles en Neuroendocrinologie, INSERM U 501 Faculté de Médecine Nord, Bd P. Dramard 13916 cedex 20, Marseille, France. becquet.d@jean-roche.univ-mrs.fr
Guillaumond
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F
Bosler
O
O
François-Bellan
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AM
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005246:Feedback; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D011333:Pro-Opiomelanocortin / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone