Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcriptional activation by nuclear hormone receptors is mediated by the 160-kDa family of nuclear receptor coactivators. These coactivators associate with DNA-bound nuclear receptors and transmit activating signals to the transcription machinery through two activation domains. In screening for mammalian proteins that bind the C-terminal activation domain of the nuclear receptor coactivator GRIP1, we identified a new variant of mouse Zac1 which we call mZac1b. Zac1 was previously discovered as a putative transcriptional activator involved in regulation of apoptosis and the cell cycle. In yeast two-hybrid assays and in vitro, mZac1b bound to GRIP1, to CREB-binding protein (CBP) and p300 (which are coactivators for nuclear receptors and other transcriptional activators), and to nuclear receptors themselves in a hormone-independent manner. In transient-transfection assays mZac1b exhibited a transcriptional activation activity when fused with the Gal4 DNA binding domain, and it enhanced transcriptional activation by the Gal4 DNA binding domain fused to GRIP1 or CBP fragments. More importantly, mZac1b was a powerful coactivator for the hormone-dependent activity of nuclear receptors, including androgen, estrogen, glucocorticoid, and thyroid hormone receptors. However, with some reporter genes and in some cell lines mZac1b acted as a repressor rather than a coactivator of nuclear receptor activity. Thus, mZac1b can interact with nuclear receptors and their coactivators and play both positive and negative roles in regulating nuclear receptor function.
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PMID:Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors. 1066 60

beta-Catenin, a pivotal component of the Wnt-signaling pathway, binds to and serves as a transcriptional coactivator for the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcriptional activator proteins and for the androgen receptor (AR), a nuclear receptor. Three components of the p160 nuclear receptor coactivator complex, including CARM1, p300/CBP, and GRIP1 (one of the p160 coactivators), bind to and cooperate with beta-catenin to enhance transcriptional activation by TCF/LEF and AR. Here we report that another component of the p160 nuclear receptor coactivator complex, the coiled-coil coactivator (CoCoA), directly binds to and cooperates synergistically with beta-catenin as a coactivator for AR and TCF/LEF. CoCoA uses different domains to bind GRIP1 and beta-catenin, and it uses different domains to transmit the activating signal to the transcription machinery, depending on whether it is bound to GRIP1 or beta-catenin. CoCoA associated specifically with the promoters of transiently transfected and endogenous target genes of TCF/LEF, and reduction of the endogenous CoCoA level decreased the ability of TCF/LEF and beta-catenin to activate transcription of transient and endogenous target genes. Thus, CoCoA uses different combinations of functional domains to serve as a physiologically relevant component of the Wnt/beta-catenin signaling pathway and the androgen signaling pathway.
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PMID:Differential use of functional domains by coiled-coil coactivator in its synergistic coactivator function with beta-catenin or GRIP1. 1634 50