![]()
|
|
||||||||
(Received for publication, May 8, 1996, and in revised form, July 2, 1996)
From the Division of Endocrinology, Diabetes, and Metabolism,
Departments of Medicine, Genetics, Pharmacology, and Biochemistry,
University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania 19104
Thyroid hormone receptors (TRs) require
heterodimerization with retinoid X receptor (RXR) for maximum DNA
binding affinity. Interaction with RXR occurs via two dimerization
interfaces, one in the DNA-binding domain and one in the C-terminal
``ninth heptad'' of the receptors. We studied the relative importance
of these two dimerization domains in naturally occurring C-terminal TR
variants. TR
Volume 271, Number 45,
Issue of November 8, 1996
pp. 28199-28205
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
1 has a conserved ninth heptad and formed stable
heterodimers with RXR in solution. TR
1·RXR heterodimers bound
similarly to direct repeat 4 (DR4) sites with different 5
-flanking and
spacer sequences. In contrast, TR
2, which contains a highly
divergent ninth heptad, did not interact with RXR in solution and
bound as a heterodimer with RXR only to specific DR4 sequences in which
the downstream half-site was the preferred octameric binding site of TR
(TNAGGTCA). Although the ninth heptad of TR
2 was insufficient for
interaction with RXR off DNA, this region was required for
DNA-dependent heterodimerization with RXR. TR
3, another
naturally occurring TR
isoform whose ninth heptad differs from those
of both TR
1 and TR
2, displayed intermediate behavior in
heterodimerization with RXR. Thus, in the absence of a strong ninth
heptad interaction an octameric downstream half-site
allosterically promotes RXR heterodimerization with TR
2.
Differential dependence upon DNA-binding for heterodimerization with
RXR may influence transcriptional regulation by TR
isoforms.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
K.-H. Lin, W.-J. Wang, Y.-H. Wu, and S.-Y. Cheng Activation of Antimetastatic Nm23-H1 Gene Expression by Estrogen and Its {alpha}-Receptor Endocrinology, February 1, 2002; 143(2): 467 - 475. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. H. Jho, N. Radoja, M. J. Im, and M. Tomic-Canic Negative Response Elements in Keratin Genes Mediate Transcriptional Repression and the Cross-talk among Nuclear Receptors J. Biol. Chem., November 30, 2001; 276(49): 45914 - 45920. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Ng, A. Rusch, L. L. Amma, K. Nordstrom, L. C. Erway, B. Vennstrom, and D. Forrest Suppression of the deafness and thyroid dysfunction in Thrb-null mice by an independent mutation in the Thra thyroid hormone receptor {alpha} gene Hum. Mol. Genet., November 1, 2001; 10(23): 2701 - 2708. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Yen Physiological and Molecular Basis of Thyroid Hormone Action Physiol Rev, July 1, 2001; 81(3): 1097 - 1142. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Göthe, Z. Wang, L. Ng, J. M. Kindblom, A. C. Barros, C. Ohlsson, B. Vennström, and D. Forrest Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation Genes & Dev., May 15, 1999; 13(10): 1329 - 1341. [Abstract] [Full Text] |
||||
![]() |
Y. Wu, Y.-Z. Yang, and R. J. Koenig Protein-Protein Interaction Domains and the Heterodimerization of Thyroid Hormone Receptor Variant {alpha}2 with Retinoid X Receptors Mol. Endocrinol., October 1, 1998; 12(10): 1542 - 1550. [Abstract] [Full Text] |
||||
![]() |
T. Tagami, P. Kopp, W. Johnson, O. K. Arseven, and J. L. Jameson The Thyroid Hormone Receptor Variant {alpha}2 Is a Weak Antagonist because It Is Deficient in Interactions with Nuclear Receptor Corepressors Endocrinology, May 1, 1998; 139(5): 2535 - 2544. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Farsetti, J. Lazar, M. Phyillaier, R. Lippoldt, A. Pontecorvi, and V. M. Nikodem Active Repression by Thyroid Hormone Receptor Splicing Variant {alpha}2 Requires Specific Regulatory Elements in the Context of Native Triiodothyronine-Regulated Gene Promoters Endocrinology, November 1, 1997; 138(11): 4705 - 4712. [Abstract] [Full Text] [PDF] |
||||
![]() |
I Zamir, J Zhang, and M A Lazar Stoichiometric and steric principles governing repression by nuclear hormone receptors. Genes & Dev., April 1, 1997; 11(7): 835 - 846. [Abstract] [PDF] |
||||
![]() |
Q. Shen and J. S. Subauste Dimerization Interfaces of v-ErbA Homodimers and Heterodimers with Retinoid X Receptor alpha J. Biol. Chem., December 22, 2000; 275(52): 41018 - 41027. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |