A novel mechanism of action for v-ErbA: abrogation of the inactivation of transcription factor AP-1 by retinoic acid and thyroid hormone receptors.
Ligand-activated retinoic acid receptor alpha (RAR alpha) and c-ErbA alpha repress the AP-1-mediated transcriptional activation of the interstitial collagenase gene promoter by specifically decreasing the activity of the AP-1 transcription factor. On the other hand, the v-ErbA oncoprotein fails to repress the AP-1 activity and acts as a dominant negative oncoprotein by overcoming the repression of the AP-1 activity induced by RAR alpha and c-ErbA alpha. This maintenance by v-ErbA of a fully active AP-1 complex is correlated with the abrogation by this same oncogene product of the growth-inhibitory response of chicken embryo fibroblasts to retinoic acid treatment. This new mechanism of action of v-ErbA together with its previously discovered dominant repressor effect on transcription of thyroid hormone-activated target genes may explain the contribution of the v-erbA oncogene to sarcomatogenic and leukemogenic transformation.
Immuno-Virologie Moléculaire et Cellulaire Université Claude Bernard Lyon-1/CNRS UMR30, Faculté de Médecine Alexis Carrel, Lyon, France.
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Desbois
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Aubert
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Legrand
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Pain
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Samarut
D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D003012:Microbial Collagenase / Q000235:genetics; D018774:Oncogene Proteins v-erbA; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology
D002352:Carrier Proteins; D008024:Ligands; D018774:Oncogene Proteins v-erbA; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D015682:Retroviridae Proteins, Oncogenic; D014212:Tretinoin; D003012:Microbial Collagenase