V-erba homodimers mediate the potent dominant negative activity of v-erba on everted repeats.
The oncoprotein v-erbA is a mutated form of TRalpha1 that is unable to bind thyroid hormone (T3). V-erbA homodimerizes or heterodimerizes with retinoid X receptor (RXR) on core motifs arranged as direct, everted, or inverted repeats (DRs, ERs, or IRs). We created a series of v-erbA mutants in order to obtain a better understanding of the role of v-erbA homodimers versus v-erbA-RXR heterodimers in the dominant negative activity of v-erbA on ERs (the most potent v-erbA response elements). We found that one of these mutants, v-erbA mutant E325A, is able to homodimerize but unable to heterodimerize with RXR on ERs. Our data also suggest that v-erbA homodimers interact preferentially with the corepressor NCoR over SMRT and that the interaction with corepressors is stronger with v-erbA homodimers over v-erbA-RXR heterodimers. Furthermore, functional studies showed that v-erbA homodimers rather than v-erbA-RXR heterodimers mediate the dominant negative activity of v-erbA on ERs.
Zubkova
Inna
I
G. V Montgomery Veterans Administration Medical Center and Division of Endocrinology and Metabolism, University of Mississippi, Jackson, MS 39216, USA.
Subauste
Jose S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D002522:Chlorocebus aethiops; D019281:Dimerization; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018774:Oncogene Proteins v-erbA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D020218:Response Elements; D047490:Retinoid X Receptor alpha / Q000737:chemistry / Q000378:metabolism
D018774:Oncogene Proteins v-erbA; D012097:Repressor Proteins; D047490:Retinoid X Receptor alpha