Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retinoid X receptor (RXR) participates in a wide array of hormonal signaling pathways, either as a homodimer or as a heterodimer, with other members of the steroid and thyroid hormone receptor superfamily. In this report the ligand-dependent transactivation function of RXR has been characterized, and the ability of RXR to interact with components of the basal transcription machinery has been examined. In vivo and in vitro experiments indicate the RXR ligand-binding domain makes a direct, specific, and ligand-dependent contact with a highly conserved region of the TATA-binding protein. The ability of mutations that reduce ligand-dependent transcription by RXR to disrupt the RXR-TATA-binding protein interaction in vivo and in vitro suggests that RXR makes direct contact with the basal transcription machinery to achieve activation.
 ...
PMID:Interactions between the retinoid X receptor and a conserved region of the TATA-binding protein mediate hormone-dependent transactivation. 766 83

The thyroid hormone receptor (TR) belongs to the steroid/nuclear receptor superfamily of ligand-inducible transcription factors. Numerous studies using transient transfection assays have demonstrated that in the absence of thyroid hormone (T3), unliganded TR acts as a constitutive repressor of transcription on genes bearing TR-response elements. We examined the molecular mechanism of TR repression in vitro using both HeLa nuclear extracts and purified basal factors. Here, we show that unliganded TR is an active transcriptional repressor, distinct from passive repressors that compete with activators for DNA binding. Repression by TR can be relieved by adding the T3 analog triiodothyroactic acid, suggesting that liganded TR undergoes a conformational change that masks or disrupts the repressor function. Repression by TR is mediated through the basal transcription machinery and can occur independently of previously characterized TATA-binding protein-associated cofactors thought to be involved in either basal repression or activator-dependent transcription. TR inhibits transcription at an early step during preinitiation complex (PIC) assembly, as preassembled PICs are refractory to the inhibitory effects of TR.
 ...
PMID:Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. 839 77

Unliganded human thyroid hormone receptor alpha (hTR alpha) can repress transcription by inhibiting the formation of a functional preinitiation complex (PIC) on promoters bearing thyroid hormone receptor (TR)-binding elements. Here we demonstrate that hTR alpha directly contacts the TATA-binding protein (TBP) and that preincubation of hTR alpha with TBP completely alleviates TR-mediated repression in vitro. Using stepwise preassembled PICs, we show that hTR alpha targets either the TBP/TFIIA or the TBP/TFIIA/TFIIB steps of PIC assembly for repression. We also show that the repression domain of hTR alpha maps to the C-terminal ligand-binding region and that direct TR-TBP interactions can be inhibited by thyroid hormone. Together, these results suggest a model in which unliganded hTR alpha contacts promoter-bound TBP and interferes with later steps in the initiation of transcription.
 ...
PMID:Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression. 852 5