Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator.
Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that regulate target gene transcription. The conserved carboxy-terminal region of the ligand-binding domain (AF-2) has been thought to play a critical role in mediating ligand-dependent transactivation by the interaction with coactivator(s). Using bacterially-expressed TR as a probe, far-Western-based expression cDNA library screening identified cDNAs that encode, in part, the recently reported partial steroid receptor coactivator-1 (SRC-1) sequence. Additional work, including 5' RACE, has characterized a full-length cDNA that encodes a approximately 160 kD protein as a putative thyroid hormone receptor coactivator (F-SRC-1). In vitro binding studies show that F-SRC-1 binds to a variety of nuclear hormone receptors in a ligand-dependent manner, along with TBP and TFIIB, suggesting that F-SRC-1 may play a role as a bridging molecule between nuclear hormone receptors and general transcription factors. Interestingly, AF-2 mutants also retain ligand-dependent interaction with F-SRC-1. Although F-SRC-1 recognizes the ligand-induced conformational changes of nuclear hormone receptors, our observations suggest that F-SRC-1 may bind directly with subregion(s) in nuclear hormone receptors other than the AF-2 region.
Takeshita
A
A
Department of Medicine, Brigham a Women's Hospital, Boston, MA, USA.
Yen
P M
PM
Misiti
S
S
Cardona
G R
GR
Liu
Y
Y
Chin
W W
WW
D000595:Amino Acid Sequence; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D051548:Histone Acetyltransferases; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D056920:Nuclear Receptor Coactivator 1; D011956:Receptors, Cell Surface / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
D018076:DNA, Complementary; D015335:Molecular Probes; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1