PMID- 9773977
OWN - NLM
STAT- MEDLINE
DCOM- 19981221
LR  - 20071114
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 12
IP  - 10
DP  - 1998 Oct
TI  - Protein-protein interaction domains and the heterodimerization of thyroid hormone 
      receptor variant alpha2 with retinoid X receptors.
PG  - 1542-50
AB  - Heterodimerization between thyroid hormone receptors (TRs) and retinoid X 
      receptors (RXRs) is mediated by a weak dimerization interface within the DNA- 
      binding domains (DBDs) and a strong interface within the C-terminal ligand- 
      binding domains of the receptors. Previous studies have shown that the conserved 
      ninth heptad in the TR ligand-binding domain appears to play a critical role in 
      heterodimerization with RXR. However, despite lacking the full ninth heptad, TR 
      variant alpha2 (TRv alpha2) can heterodimerize with RXR on specific direct repeat 
      response elements, but not on palindromic elements or in solution. Two 
      possibilities may account for TRv alpha2-RXR heterodimerization on direct 
      repeats. First, the DBD of TRv alpha2 may play a critical role in 
      heterodimerization with RXR. Second, a specific sequence within the unique C 
      terminus of TRv alpha2 may promote the formation of TRv alpha2-RXR heterodimers. 
      In this study, we used receptor chimeras in which the DBD of RXR was replaced by 
      either the TR DBD or an unrelated DBD from the metalloregulatory transcription 
      factor AMT1 to address the role of the DBD dimerization interface in TRv 
      alpha2-RXR heterodimerization. Gel mobility shift analyses showed that whereas TR 
      alpha1 formed heterodimers with these chimeras, TRv alpha2 failed to do so. 
      Deletion of the unique C terminus of TRv alpha2 had only a marginal effect on 
      heterodimerization with RXR. Mutations within the DBD dimerization interface 
      abolished heterodimerization of full-length TRv alpha2 with RXR but only 
      marginally affected heterodimerization of full-length TR alpha1 with RXR. These 
      data support the hypothesis that the TR-RXR DBD dimerization interface plays a 
      critical role in TRv alpha2-RXR heterodimerization. Additional data show that the 
      amino acid residues that make direct TR-RXR contacts within the DBDs also may 
      play a role in receptor monomer binding to DNA, since mutations within these 
      residues severely impair this interaction.
FAU - Wu, Y
AU  - Wu Y
AD  - Division of Endocrinology and Metabolism, University of Michigan Medical Center, 
      Ann Arbor 48109-0678, USA.
FAU - Yang, Y Z
AU  - Yang YZ
FAU - Koenig, R J
AU  - Koenig RJ
LA  - eng
GR  - DK-44155/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - DNA/metabolism
MH  - Dimerization
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Receptors, Retinoic Acid/chemistry/genetics/*metabolism
MH  - Receptors, Thyroid Hormone/*chemistry/genetics/*metabolism
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Response Elements
MH  - Retinoid X Receptors
MH  - Transcription Factors/chemistry/genetics/*metabolism
EDAT- 1998/10/17 00:00
MHDA- 1998/10/17 00:01
CRDT- 1998/10/17 00:00
PHST- 1998/10/17 00:00 [pubmed]
PHST- 1998/10/17 00:01 [medline]
PHST- 1998/10/17 00:00 [entrez]
AID - 10.1210/mend.12.10.0178 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1998 Oct;12(10):1542-50. doi: 10.1210/mend.12.10.0178.