Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human placental lactogen B (hCS-B) promoter activity is strongly stimulated by triiodothyronine (T3) in pituitary GC cells through interaction between the thyroid receptor and a thyroid receptor-binding element (TBE) spanning coordinates -67 to -41. This TBE is adjacent to the binding site for pituitary factor GHF1 (-95 to -68) which seems necessary for T3 stimulation of hCS-B promoter activity (M. L. Voz, B. Peers, A. Belayew, and J. A. Martial, J. Biol. Chem. 266:13397-13404, 1991). We here demonstrate actual synergy between the thyroid receptor and GHF1. Indeed, in placental JEG-3 cells devoid of factor GHF1, hCS promoter activity is barely stimulated by T3, while a strong response is observed in pituitary GC cells. In the latter, furthermore, neither the TBE nor the GHF1-binding site alone is sufficient to render the thymidine kinase promoter responsive to T3, while in combination they promote strong T3 stimulation. Close proximity between these sites is required for optimal synergy: T3 stimulation globally decreases with increased spacing. Furthermore, synergy occurs not only with a GHF1-binding site but also with all other factor recognition sequences tested (Sp1, NF1, CP1, Oct1, and CACCC boxes) and even with two other copies of the TBE. Nor is it specific to hCS TBE, since the palindromic sequence TCAGGTCA TGACCTGA (TREpal) also exhibits cooperativity.
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PMID:Transcriptional regulation by triiodothyronine requires synergistic action of the thyroid receptor with another trans-acting factor. 132 11

The promoter of the human thymidine kinase gene contains cis-regulatory elements responsible for its cell-cycle-regulated expression. We report here that a 70-bp region between -133 and -64 is sufficient to confer cell cycle regulation on a heterologous promoter. The 20-bp region between -64 and -83, which contains an inverted CCAAT motif, is important for transcriptional stimulation of this functional unit. The sequence of this CCAAT motif is nearly identical to the consensus sequence for the transcriptional factor CP1. We also examined the specificity and binding activities of cellular factors interacting with the 70-bp fragment. We showed that the cellular factors binding to the 70-bp region are similar during the G1, S, and G2 phases, suggesting that the cell cycle regulatory activity observed must involve processes other than factor binding to the DNA.
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PMID:Identification of a 70-base-pair cell cycle regulatory unit within the promoter of the human thymidine kinase gene and its interaction with cellular factors. 200 12

Regulated synthesis of luteinizing hormone (LH) requires coordinated transcriptional control of the alpha and LHbeta subunits in pituitary gonadotropes. Several cis-acting elements and trans-acting factors have been defined for control of the LHbeta promoter through heterologous cell culture models. In this report, we describe the identification of bipartite NF-Y (CBF/CP1) binding sites within the proximal bovine LHbeta promoter. When multimerized, one of these sites activates the heterologous, minimal HSV thymidine kinase promoter in the gonadotrope-derived cell line alphaT3-1. The functional role of the promoter-distal site in regulating the full-length bovine LHbeta promoter was assessed in vivo using transgenic mice harboring a mutant promoter linked to the chloramphenicol acetyltransferase reporter gene. While this element is important for conferring high level activity of the LHbeta promoter in pituitary, it does not appear to be essential for mediating gonadotropin-releasing hormone (GnRH) regulation. This is the first characterization of a cis-acting element within this GnRH-dependent promoter that is restricted to regulating basal expression and not GnRH-induced activity.
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PMID:An NF-Y binding site is important for basal, but not gonadotropin-releasing hormone-stimulated, expression of the luteinizing hormone beta subunit gene. 1077 13