Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator.
Nuclear hormone receptors activate gene transcription through ligand-dependent association with coactivators. Specific LXXLL sequence motifs present in these cofactors are sufficient to mediate these ligand-induced interactions. A thyroid hormone receptor (TR)-binding protein (TRBP) was cloned by a Sos-Ras yeast two-hybrid system using TRbeta1-ligand binding domain as bait. TRBP contains 2063 amino acid residues, associates with TR through a LXXLL motif, and is ubiquitously expressed in a variety of tissues and cells. TRBP strongly transactivates through TRbeta1 and estrogen receptor in a dose-related and ligand-dependent manner, and also exhibits coactivation through AP-1, CRE, and NFkappaB-response elements, similar to the general coactivator CBP/p300. The C terminus of TRBP binds to CBP/p300 and DRIP130, a component of the DRIP/TRAP/ARC complex, which suggests that TRBP may activate transcription by means of such interactions. Further, the association of TRBP with the DNA-dependent protein kinase (DNA-PK) complex and DNA-independent phosphorylation of TRBP C terminus by DNA-PK point to a potential connection between transcriptional control and chromatin architecture regulation.
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Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D050882:CREB-Binding Protein; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D056892:Mediator Complex; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D056918:Nuclear Receptor Coactivators; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; C113182:DRIP, VDR interacting protein complex; D047908:Intracellular Signaling Peptides and Proteins; C492159:MED23 protein, human; C491863:MED4 protein, human; D056892:Mediator Complex; C486559:NCOA6 protein, human; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases