A novel multifunctional motif in the amino-terminal A/B domain of T3Ralpha modulates DNA binding and receptor dimerization.

The Journal of Biological Chemistry
E HadzicH H Samuels

Abstract

We reported previously that deletion of the 50-amino acid NH2-terminal A/B domain of the chicken (c) or rat thyroid hormone (T3) receptor-alpha (T3Ralpha) decreased the T3-dependent stimulation of genes regulated by native thyroid hormone response elements (TREs). This requirement of the NH2-terminal A/B domain for transcriptional activation was mapped to amino acids 21-30 of cT3Ralpha. Expression of transcription factor IIB (TFIIB) in cells was shown to enhance T3-dependent transcriptional activation by cT3Ralpha, and this enhancement by TFIIB was dependent on the same 10-amino acid sequence. In vitro binding studies indicated that cT3Ralpha interacts efficiently with TFIIB, and this interaction requires amino acids 23KRKRK27 in the A/B domain. In this study we document the functional importance of these five basic residues in transcriptional activation by cT3Ralpha, further supporting the biological significance of these residues and their interaction with TFIIB. Interestingly, we also find that the same amino acids also affect DNA binding and dimerization of cT3Ralpha. Gel mobility shift assays reveal that a cT3Ralpha mutant that has all five basic amino acids changed from 23KRKRK27 to 23TITIT27 binds to a palindromic TRE pr...Continue Reading

References

May 1, 1992·Endocrine Reviews·L P Freedman
Sep 1, 1990·Molecular Endocrinology·B M Forman, H H Samuels
Jan 1, 1990·Methods in Enzymology·F W StudierJ W Dubendorff
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M A LazarW W Chin
Dec 18, 1986·Nature·C WeinbergerR M Evans
Sep 1, 1982·Molecular and Cellular Biology·C M GormanB H Howard
Dec 14, 1995·Nature·R L WagnerR J Fletterick
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·H TomuraV M Nikodem
Jan 17, 1995·Proceedings of the National Academy of Sciences of the United States of America·H Chen, M L Privalsky
Dec 15, 1995·Cell·D J Mangelsdorf, R M Evans

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Citations

Jul 31, 2001·Molecular and Cellular Endocrinology·T MiyamotoK Hashizume
Feb 13, 2003·Molecular and Cellular Endocrinology·Inna Zubkova, Jose S Subauste
Mar 15, 2001·European Journal of Biochemistry·J F MouilletM Vögtli
Jul 21, 2012·The Journal of Biological Chemistry·Manohara S MavinakereLizabeth A Allison
Jun 9, 2000·Annual Review of Physiology·J Zhang, M A Lazar
Dec 1, 2004·The Journal of Cell Biology·Nuttawut SaelimJames D Lechleiter
Oct 6, 2000·The Journal of Biological Chemistry·Q Shen, J S Subauste
Jan 15, 2000·The Journal of Biological Chemistry·C Oberste-BerghausF E Wondisford
Jun 28, 2001·Physiological Reviews·P M Yen

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