PMID- 1850111
OWN - NLM
STAT- MEDLINE
DCOM- 19910523
LR  - 20081121
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 5
IP  - 1
DP  - 1991 Jan
TI  - 3,5,3'-triiodothyronine (T3) receptor-auxiliary protein (TRAP) binds DNA and 
      forms heterodimers with the T3 receptor.
PG  - 73-84
AB  - Nuclear factors enhance binding of T3 receptors (TR) to DNA, suggesting that T3 
      action may require a multicomponent complex bound to thyroid hormone response 
      elements (TREs). We refer to the 65,000 Da nuclear protein in GH3 cells that 
      enhances TR binding to DNA as the TR-auxiliary protein (TRAP) and have 
      characterized its interaction with TR. Using a TRE-DNA affinity matrix we show 
      that TRAP is able to bind to DNA, even in the absence of functional TR. We then 
      used carboxyl-terminal truncations of rat TR alpha-1 and human TR beta in the 
      avidin-biotin complex DNA-binding assay to identify regions that are important 
      for interaction with TRAP. Removal of 34 residues of hTR beta abolishes 
      T3-binding activity, but the ability to bind TRAP is retained. Further 
      truncations and point mutations suggest that TRAP interacts with the 
      ligand-binding domain of TR and with an independent region which overlaps a 
      conserved sequence adjacent to the second Zn2+ finger (amino acids 120-149 in rTR 
      alpha-1). A fragment of rTR alpha-1 (alpha C291) which encompasses these two 
      regions inhibits the ability of TRAP to enhance TR binding to DNA. This is due to 
      binding of alpha C291 to TR, demonstrating the ability of TR to form homodimers. 
      The inability of TRAP to interact with TR dimers and the similarity of the 
      locations of the estradiol receptor dimerization domains with the TRAP 
      interaction regions lead us to conclude that TRAP stabilizes TR binding to DNA by 
      formation of TRAP-TR heterodimers with both proteins bound to the DNA. TR bound 
      to the estrogen response element is unable to respond to TRAP and unable to 
      stimulate transcription, possibly due to the absence of TRAP in the TR-estrogen 
      response element complex. In addition, TRAP may interact with a certain subset of 
      the nuclear receptor superfamily, since human retinoic acid receptor-beta and 
      vitamin D receptor show increased binding to TREs in the presence of nuclear 
      extract, but c-erbA alpha-2, a variant TR, does not respond to TRAP.
FAU - Darling, D S
AU  - Darling DS
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 
      02115.
FAU - Beebe, J S
AU  - Beebe JS
FAU - Burnside, J
AU  - Burnside J
FAU - Winslow, E R
AU  - Winslow ER
FAU - Chin, W W
AU  - Chin WW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Carrier Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Estradiol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Carrier Proteins/metabolism
MH  - Cell Line
MH  - Cell Nucleus/chemistry
MH  - Chromatography, Affinity
MH  - DNA/*metabolism
MH  - Genetic Variation
MH  - Humans
MH  - Macromolecular Substances
MH  - Molecular Weight
MH  - Mutagenesis
MH  - Nuclear Proteins/*metabolism
MH  - Peptide Fragments/metabolism
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins/genetics
MH  - Rats
MH  - Receptors, Calcitriol
MH  - Receptors, Estradiol/metabolism
MH  - Receptors, Retinoic Acid
MH  - Receptors, Steroid/metabolism
MH  - Receptors, Thyroid Hormone/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Zinc Fingers
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
AID - 10.1210/mend-5-1-73 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1991 Jan;5(1):73-84. doi: 10.1210/mend-5-1-73.