A novel cis element mediating ligand-independent activation by c-ErbA: implications for hormonal regulation.
A novel type of hormone-responsive element (HRE) is described. Unlike classical HREs, this element, RSV-T3RE (found in Rous sarcoma virus-long terminal repeat), mediates strong activation by the c-ErbA alpha thyroid hormone (T3) receptor in the absence of T3, and addition of T3 reverses this response. Whereas both c-ErbA alpha and v-ErbA are potent ligand-independent activators through the RSV-T3RE, c-ErbA beta is not. The RSV-T3RE is recognized and activated by either c-ErbA alpha homodimers or c-ErbA alpha/retinoid X receptor (RXR) heterodimers. Ligand-independent activation by c-ErbA alpha depends on a unique N-terminal activation domain, while the C-terminal activation domain is not absolutely required. Ligand-dependent activation, on the other hand, requires the C-terminal but not the N-terminal activation domain. Upon binding to the RSV-T3RE, c-ErbA alpha assumes a different conformation than when bound to a classical T3RE. c-ErbA alpha is therefore capable of selective deployment of activation domains, dictated both by the HRE with which it interacts and by T3 binding.
Saatcioglu
F
F
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.
Deng
T
T
Karin
M
M
D000478:Alkylation; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D007700:Kinetics; D008745:Methylation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D018774:Oncogene Proteins v-erbA; D011401:Promoter Regions, Genetic; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D015682:Retroviridae Proteins, Oncogenic; D014284:Triiodothyronine