PMID- 10375023
OWN - NLM
STAT- MEDLINE
DCOM- 19990820
LR  - 20190813
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 149
IP  - 1-2
DP  - 1999 Mar 25
TI  - Dominant negative activity of thyroid hormone receptor variant alpha2 and 
      interaction with nuclear corepressors.
PG  - 107-14
AB  - The splicing variant of the thyroid hormone receptor alpha (TRalpha) gene, TR 
      variant alpha2 (TRv alpha2), lacks the second half of the ninth heptad, a domain 
      thought to be important for heterodimerization with retinoid X receptors (RXRs). 
      In transient transfection studies, TRv alpha2 exhibits weak dominant negative 
      inhibition of TRalpha1-mediated transcription. In contrast, a TRv alpha2 mutant 
      in which the ninth heptad was restored (alpha2 + 9H), exhibits very strong 
      dominant negative activity. We have examined the role of nuclear corepressors 
      (CoRs) in the dominant negative activity of TRv alpha2 and alpha2 + 9H. 
      Glutathione S-transferase pull down experiments revealed that TRv alpha2 barely 
      interacts with CoRs, whereas alpha2 + 9H interaction with CoRs is as strong as 
      that of TRalpha1. A P160R CoR box mutation was introduced in the context of TRv 
      alpha2 and alpha2 + 9H, which nearly abolishes the ability of these receptors to 
      interact with CoRs. In transient transfection the dominant negative activity of 
      TRv alpha2 was only marginally impaired by the P160R mutation. In contrast, 
      alpha2 + 9H-P160R had approximately 66% less dominant negative activity than 
      alpha2 + 9H. These results suggest that the weak dominant negative activity of 
      TRv alpha2 is due in part to its lack of interaction with CoRs, and that 
      restoration of the ninth heptad restores CoR interaction and strong dominant 
      negative activity. Further, the data reveal aspects of the dominant negative 
      action that are dependent on the orientation of the TRE.
FAU - Burgos-Trinidad, M
AU  - Burgos-Trinidad M
AD  - Division of Endocrinology and Metabolism, University of Michigan Medical Center, 
      Ann Arbor 48109-0678, USA.
FAU - Koenig, R J
AU  - Koenig RJ
LA  - eng
GR  - DK44155/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (DNA Primers)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - Genetic Variation
MH  - Mice
MH  - Mutation
MH  - Nuclear Proteins/metabolism
MH  - Rats
MH  - Receptors, Thyroid Hormone/*genetics/*metabolism
MH  - Repressor Proteins/*metabolism
MH  - Transfection
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - S0303-7207(98)00253-6 [pii]
AID - 10.1016/s0303-7207(98)00253-6 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 1999 Mar 25;149(1-2):107-14. doi: 
      10.1016/s0303-7207(98)00253-6.