Activation and repression of growth factor receptor gene transcription (Review).
Growth factor receptors mediate cell signaling events that regulate a diverse array of cellular activities including cell proliferation, homeostasis, and differentiation of both normal and cancer cells. Studies of the mechanisms governing transcription of growth factor receptor genes have revealed common structural features of their promoters. These common features include GC rich promoter regions and multiple Sp factor binding sites based upon which most of these promoters are transactivated. Mechanisms of growth factor receptor promoter activation via these common structural features will be reviewed, with particular attention to control of FGFR1 promoter activity in skeletal muscle cells. Of equal importance in cellular function is the repression of growth factor receptor signaling and gene expression. Mechanisms that repress growth factor receptor promoter activity operate via direct repression at transcriptional activator binding sites and via protein-protein interactions that abrogate activator function. Mechanisms of growth factor receptor transcriptional repression will be considered in the context of known tumor suppressors, transcription activator availability, as well as in light of emerging potential Sp1-like transcriptional repressors.
DiMario
Joseph X
JX
Department of Cell Biology and Anatomy, Chicago Medical School, North Chicago, IL 60064, USA. dimarioj@finchcms.edu
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000502:physiology
D004268:DNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1