Dimerization of v-erbA on inverted repeats.
Thyroid hormone receptors (TRs) and the oncoprotein v-erbA can heterodimerize with retinoid X receptor (RXR) on core motifs arranged as inverted repeats (IR0) which contain the consensus sequence AGGTCA. On this core motif, v-erbA can also form homodimers whereas TRs homodimerize very poorly. Therefore to obtain a better understanding of distinct homodimerization properties of TR alpha 1 as compared to those of v-erbA, we created chimeras between these two receptors and tested their abilities to homodimerize on IR0. We found that the enhanced homodimerization properties of v-erbA compared to those of TR alpha 1 on IR0 map to amino acids 107-156 in v-erbA/121-170 in TR alpha 1 (VT-2 chimera). Furthermore, functional studies on transient transfections showed that v-erbA-RXR heterodimers do not mediate the dominant negative activity of v-erbA on an inverted repeat response element. These data, in conjunction with our previous studies, indicate that v-erbA homodimers mediate the repressor activity of v-erbA on IR0.
Zubkova
Inna
I
Division of Endocrinology and Metabolism, Department of Medicine, G.V. Montgomery Veterans Administration Medical Center, University of Mississippi, Jackson, MS 39216, USA.
Subauste
Jose S
JS
D000818:Animals; D002460:Cell Line; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D016297:Mutagenesis, Site-Directed; D018774:Oncogene Proteins v-erbA / Q000737:chemistry* / Q000235:genetics; D017354:Point Mutation; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D013329:Structure-Activity Relationship; D037021:Thyroid Hormone Receptors alpha; D014157:Transcription Factors / Q000378:metabolism
D018774:Oncogene Proteins v-erbA; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D037021:Thyroid Hormone Receptors alpha; D014157:Transcription Factors