title: At least three subdomains of v-erbA are involved in its silencing function.
abstract: Several members of the thyroid hormone receptor (TR) family are able to switch from a transcriptional repressor to a transcriptional activator upon binding of their ligand. The oncogene v-erbA is a variant form of the TR unable to bind hormone and thus acts as a constitutive repressor. We demonstrate, using fusion proteins between the DNA-binding domain of the yeast factor GAL4 and the silencing domains of v-erbA and TR beta, that point mutations in three different regions severely affect their repression function. Furthermore, the three regions, each as an inactive fusion protein with the GAL4 DNA-binding domain, restore silencing activity when assembled on the same promoter. These observations define at least three silencing subdomains, SSD1-SSD3, which are involved in the silencing function of v-erbA. We propose a model in which full silencing activity is brought about by the combined interaction of each silencing subdomain with corepressors and/or basal transcription factors.
authors.affiliation: Laboratoire de Biologie Moléculaire et de Génie Génétique, Université de Liège, Sart-Tilman, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Busch
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Baniahmad
authors.forename: R
authors.initials: R
authors.lastname: Renkawitz
authors.forename: M
authors.initials: M
authors.lastname: Muller
mesh_terms: D000595:Amino Acid Sequence; D001667:Binding, Competitive; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018774:Oncogene Proteins v-erbA / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014162:Transfection
chemical_list: D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors