A NOVEL MECHANISM OF ACTION FOR V-ERBA - ABROGATION OF THE INACTIVATION OF TRANSCRIPTION FACTOR AP-1 BY RETINOIC ACID AND THYROID-HORMONE RECEPTORS

被引:158
作者
DESBOIS, C [1 ]
AUBERT, D [1 ]
LEGRAND, C [1 ]
PAIN, B [1 ]
SAMARUT, J [1 ]
机构
[1] ECOLE NORMALE SUPER LYON,INRA,BIOL MOLEC & CELLULAIRE LAB,CNRS,UMR49,F-69364 LYONS 07,FRANCE
关键词
D O I
10.1016/0092-8674(91)90068-A
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:731 / 740
页数:10
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