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

Sodium butyrate has been shown to exert dramatic effects on the growth of cells in culture. It inhibits DNA synthesis, arrests actively proliferating cells in G1 and induces differentiation. The mechanism responsible for these various anti-proliferative effects is presently unknown. We wished to study the effects of sodium butyrate on cell growth at the molecular level, by analyzing the pattern of expression exhibited by several growth-associated genes (e.g., c-fos, c-myc, p53 and thymidine kinase) in Swiss 3T3 cells following treatment with sodium butyrate. Our results suggest that sodium butyrate-induced growth arrest of Swiss 3T3 cells (1) can be distinguished at a molecular level from the arrest brought about by other means of growth arrest; (2) does not result from a generalized mechanism which non-specifically shuts down the expression of growth-associated genes but rather occurs via a more specific mechanism which leads to the reduction in the expression of certain genes (e.g., c-myc, p53, thymidine kinase) while inducing the expression of others (e.g., c-fos, aP2); and (3) may involve one or more of the molecular events leading to adipocyte differentiation.
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PMID:Molecular analysis of sodium butyrate-induced growth arrest. 314 95

Sodium butyrate causes alteration of colon cancer cell morphology and biology towards that of a more differentiated phenotype. The retinoblastoma gene encodes a nuclear phosphoprotein (pRb) present in a wide range of human cancer cell lines including colon cancer cell lines. pRB is synthesized throughout the cell cycle and phosphorylated in a phase specific manner: the predominant proteins in G0/G1 are the unphosphorylated species (110 kD) whereas phosphorylated pRb (112-114 kD) are in S and G2. 110 kD pRb binds transcription factors and prevents transcription of responsive genes such as the gene for thymidine kinase, which are expressed in late G1. The precise mechanisms controlling cell arrest are unknown, but recent data suggest that cyclin-dependent kinase inhibitors such as p16 may play a role. The aim of the present study was to assess the effect of sodium butyrate on cell cycle staging, thymidine kinase activity, phosphorylation of the pRb protein and expression of p16. We show that sodium butyrate treatment induces differentiation of LS174T colon cancer cells, inhibits thymidine kinase activity concomitantly with induction of pRb dephosphorylation, p16 transcription and cell cycle arrest at G0/G1. Initial dephosphorylation was observed 24 h after treatment of LS174T cells with sodium butyrate, whereas complete shift to the dephosphorylated form was observed 3 days after treatment. Induction of pRb dephosphorylation by sodium butyrate preceded inhibition of growth and the specific cell cycle arrest. RNase protection assay with a p16 specific riboprobe showed undetectable levels in proliferating cells to several fold increase in differentiated colonocytes. In conclusion, the results provide evidence for a specific cellular mechanism of butyrate induced growth arrest and differentiation of a colon cancer cell line.
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PMID:Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells. 982 7

Based on the structure of our previously identified mitochondrial thymidine kinase (TK-2) inhibitors, three series of thymine-derived carboxamides have been synthesized and tested against TK-2 and related enzymes. The methodology employed has been a solution-phase parallel synthesis based on the coupling of three thymine-derived acids [4-(thymin-1-yl)butyric acid (I), [4-(thymin-1-yl)-butyrylamino]acetic acid (II) and 6-(thymin-1-yl)hexanoic acid (III)] with different commercially available primary amines that carry cyano and/or phenyl groups. The couplings were performed in good yields (from 60% to 90%), with the exception of those that incorporate the highly crowded triphenylmethylamine (e). From the new synthesized compounds, the N-trityl-6-(thymin-1-yl)hexanamide (IIIe) was the most active TK-2 inhibitor (IC(50)=19+/-2microM).
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PMID:Synthesis and evaluation of thymine-derived carboxamides against mitochondrial thymidine kinase (TK-2) and related enzymes. 1535 91