当前位置： SCI文献检索 > BIOCHEMICAL PHARMACOLOGY期刊下所有文献 > Phosphorylation of deoxycytidine kinase on Ser-74: impact on kinetic properties and nucleoside analog activation in cancer cells.

Phosphorylation of deoxycytidine kinase on Ser-74: impact on kinetic properties and nucleoside analog activation in cancer cells.

Abstract：

:Deoxycytidine kinase (dCK) (EC 2.7.1.74) is a key enzyme in the activation of several therapeutic nucleoside analogs (NA). Its activity can be increased in vivo by Ser-74 phosphorylation, a property that could be used for enhancing NA activation and clinical efficacy. In line with this, studies with recombinant dCK showed that mimicking Ser-74 phosphorylation by a S74E mutation increases its activity toward pyrimidine analogs. However, purine analogs had not been investigated. Here, we show that the S74E mutation increased the k(cat) for cladribine (CdA) by 8- or 3-fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine (CAFdA) by about 2-fold with both ATP and UTP, and for fludarabine (F-Ara-A) by 2-fold, but only with UTP. However, the catalytic efficiencies (k(cat)/Km) were not, or slightly, increased. The S74E mutation also sensitized dCK to feed-back inhibition by dCTP, regardless of the phosphoryl donor. Importantly, we did not observe an increase of endogenous dCK activity toward purine analogs after in vivo-induced increase of Ser-74 phosphorylation. Accordingly, treatment of CLL cells with aphidicolin, which enhances dCK activity through Ser-74 phosphorylation, did not modify the conversion of CdA or F-Ara-A into their active triphosphate form. Nevertheless, the same treatment enhanced activation of gemcitabine (dFdC) into dFdCTP in CLL as well as in HCT-116 cells and produced synergistic cytotoxicity. We conclude that increasing phosphorylation of dCK on Ser-74 might constitute a valuable strategy to enhance the clinical efficacy of some NA, like dFdC, but not of CdA or F-Ara-A.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Amsailale R,Van Den Neste E,Arts A,Starczewska E,Bontemps F,Smal C

doi

10.1016/j.bcp.2012.03.022

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

43-51

issue

1

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(12)00238-9

journal_volume

84

pub_type

杂志文章

相关文献

BIOCHEMICAL PHARMACOLOGY文献大全
  • A human small cell lung carcinoma cell line, resistant to 4'-(9-acridinylamino)-methanesulfon-m-anisidide and cross-resistant to camptothecin with a high level of topoisomerase I.

    abstract：:N417/AMSA cells, about 80-fold resistant to mAMSA [4'-(9-acridinylamino)-methanesulfon-m-anisidide], were obtained by serial passages of the parental human small cell lung carcinoma NCI-N417 (N417/p) in stepwise drug concentrations. The N417/AMSA cells were found to be 114-, 100-, and 9-fold cross-resistant to the top...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(94)90368-9

    authors： Prost S,Riou G

    更新日期：1994-08-30 00:00:00

  • Modulation of ATPase activity by cholesterol and synthetic ether lipids in leukemic cells.

    abstract：:Synthetic ether lipids (EL) exert their antiproliferative action on leukemic cells through localization in the plasma membrane with subsequent biochemical effects which are still being elucidated. In the present study, the modulation of membrane-linked ATPase activity was investigated in relation to changes in membran...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(92)90246-f

    authors： Diomede L,Bianchi R,Modest EJ,Piovani B,Bubba F,Salmona M

    更新日期：1992-02-18 00:00:00

  • Molecular characterization of functional UDP-glucuronosyltransferases 1A and 2B in common marmosets.

    abstract：:UDP-glucuronosyltransferases (UGTs) are essential drug-conjugation enzymes that metabolize a variety of endobiotic and xenobiotic substrates. The molecular characteristics of UGTs have been extensively investigated in humans, but remain to be investigated in common marmosets, a nonhuman primate species widely used in ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2019.113748

    authors： Uno Y,Uehara S,Inoue T,Kawamura S,Murayama N,Nishikawa M,Ikushiro S,Sasaki E,Yamazaki H

    更新日期：2020-02-01 00:00:00

  • Regulatory roles of adenylate cyclase and cyclic nucleotide phosphodiesterases 1 and 4 in interleukin-13 production by activated human T cells.

    abstract：:We studied the activities of 3',5'-adenosine-cyclic monophosphate (cAMP)- synthesizing adenylate cyclase (AC) and cAMP-hydrolyzing cyclic nucleotide phosphodiesterase (PDE) in phytohemagglutinin (PHA)- or anti-CD3 plus anti-CD28-stimulated human T cells, and examined their roles in interleukin-13 (IL-13) production. T...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(01)00688-8

    authors： Kanda N,Watanabe S

    更新日期：2001-08-15 00:00:00

  • In vivo iron mobilisation evaluation of hydroxypyridinones in 59Fe-ferritin-loaded rat model.

    abstract：:Although there are a number of well-characterised animal models available for testing and comparing the efficacy of iron chelators, most are expensive to operate and are not capable of providing rapid and reproducible results. The method described herein is based on the labelling of rat liver with 59Fe using rat 59Fe-...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(98)00319-0

    authors： Liu ZD,Lu SL,Hider RC

    更新日期：1999-03-01 00:00:00

  • The measurement of polyglutamate metabolites of the thymidylate synthase inhibitor, ICI D1694, in mouse and human cultured cells.

    abstract：:A method is described for the measurement of the polyglutamates of the quinazoline thymidylate synthase inhibitor, N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin- 6-ylmethyl)-N-methylamino]-2-theonyl)-L-glutamic acid (ICI D1694). This involved incubation of cells with [5-3H]ICI D1694, extraction of the polyglutamates a...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(93)90170-2

    authors： Gibson W,Bisset GM,Marsham PR,Kelland LR,Judson IR,Jackman AL

    更新日期：1993-02-24 00:00:00

  • Evidence for involvement of tyrosine phosphorylation in taxol-induced apoptosis in a human ovarian tumor cell line.

    abstract：:Taxol is an antineoplastic agent with significant activity against ovarian as well as breast cancer. To investigate mechanisms by which taxol exerts its cytotoxic action, taxol-induced apoptosis, characterized by morphologic changes and internucleosomal DNA fragmentation, was examined in a human ovarian tumor cell lin...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(94)90164-3

    authors： Liu Y,Bhalla K,Hill C,Priest DG

    更新日期：1994-09-15 00:00:00

  • Substoichiometric inhibition of microtubule formation by acetaldehyde-tubulin adducts.

    abstract：:We have shown previously that acetaldehyde forms stable covalent adducts with tubulin, resulting in impaired microtubule formation. The present study explored the mechanism responsible for impaired microtubule formation caused by the substoichiometric stable binding of acetaldehyde to tubulin. The free tubulin dimer w...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(92)90039-l

    authors： Smith SL,Jennett RB,Sorrell MF,Tuma DJ

    更新日期：1992-07-07 00:00:00

  • Inhibition of ATP-induced surfactant exocytosis by dihydropyridine (DHP) derivatives: a non-stereospecific, photoactivated effect and independent of L-type Ca2+ channels.

    abstract：:Purinergic stimulation of surfactant secretion via exocytosis of lamellar bodies is mediated by an elevation of the intracellular Ca2+ concentration ([Ca2+](i)). We tested the dihydropyridine (DHP) analogues isradipine (+/-enantiomers), nifedipine and Bay K 8644 (racemic forms) on ATP-induced surfactant secretion and ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(01)00582-2

    authors： Frick M,Siber G,Haller T,Mair N,Dietl P

    更新日期：2001-05-01 00:00:00

  • Toluene metabolism by cDNA-expressed human hepatic cytochrome P450.

    abstract：:The metabolism of toluene in human liver microsomes and by cDNA-expressed human cytochrome P450s (CYPs) was investigated. Toluene was metabolized mainly to benzyl alcohol and slightly to o- and p-cresol by human liver microsomes. Formation of o-cresol was elevated in microsomes from human livers derived from cigarette...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(96)00652-1

    authors： Nakajima T,Wang RS,Elovaara E,Gonzalez FJ,Gelboin HV,Raunio H,Pelkonen O,Vainio H,Aoyama T

    更新日期：1997-02-07 00:00:00

  • The forgotten Gram-negative bacilli: what genetic determinants are telling us about the spread of antibiotic resistance.

    abstract：:Gram-negative bacilli have become increasingly resistant to antibiotics over the past 2 decades due to selective pressure from the extensive use of antibiotics in the hospital and community. In addition, these bacteria have made optimum use of their innate genetic capabilities to extensively mutate structural and regu...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.bcp.2005.11.006

    authors： Gootz TD

    更新日期：2006-03-30 00:00:00

  • Microsomal warfarin binding and vitamin K 2,3-epoxide reductase.

    abstract：:Rat liver microsomal 4-hydroxycoumarin binding was studied by assaying specific [14C]warfarin binding. Microsomes of warfarin-sensitive rats contained about 40 pmole of specific binding sites per mg of microsomal protein. There was no difference for R- or S-[14C]warfarin. Neither was there any difference between the e...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(89)90257-8

    authors： Thijssen HH,Baars LG

    更新日期：1989-04-01 00:00:00

  • LPS-induced dissociation of multidrug resistance-associated protein 2 (Mrp2) and radixin is associated with Mrp2 selective internalization in rats.

    abstract：:Multidrug resistance-associated protein 2 (Mrp2) is an ATP-dependent export pump that mediates the formation of bile-salt-independent bile flow. Disruption of the canalicular localization of Mrp2, without changes in its expression, is observed in chronic liver failure and is accompanied by oxidative stress. We reporte...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2010.09.016

    authors： Saeki J,Sekine S,Horie T

    更新日期：2011-01-01 00:00:00

  • IL-8 production by macrophages is synergistically enhanced when cigarette smoke is combined with TNF-alpha.

    abstract：:Macrophages are key inflammatory cells in chronic obstructive pulmonary disease (COPD). The pathophysiology of cigarette smoke-induced lung emphysema is complex but there is a clear role for reactive oxygen species (ROS, such as peroxynitrite), tumor necrosis factor (TNF-alpha) and interleukin (IL)-8. We investigated ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2009.10.001

    authors： Sarir H,Mortaz E,Janse WT,Givi ME,Nijkamp FP,Folkerts G

    更新日期：2010-03-01 00:00:00

  • P2X7 receptor and the NLRP3 inflammasome: Partners in crime.

    abstract：:Adenosine triphosphate (ATP) is a molecule that on one hand plays a central role in cellular energetics and which on the other is a ubiquitous signaling molecule when released into the extracellular media. Extracellular ATP accumulates in inflammatory environments where it acts as a damage-associated molecular pattern...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.bcp.2020.114385

    authors： Pelegrin P

    更新日期：2020-12-20 00:00:00

  • Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): implications for its function in biological systems.

    abstract：:Pyrroloquinoline quinone (PQQ) is a novel redox cofactor recently found in human milk. It has been reported to function as an essential nutrient, antioxidant and redox modulator in cell culture experiments and in animal models of human diseases. As mitochondria are particularly susceptible to oxidative damage we studi...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(02)01453-3

    authors： He K,Nukada H,Urakami T,Murphy MP

    更新日期：2003-01-01 00:00:00

  • Denitrosation of 1,3-dimethyl-2-cyano-1-nitrosoguanidine in rat primary hepatocyte cultures.

    abstract：:N-Nitrosoguanidines are potential carcinogens. However, the toxicity of these agents is attenuated significantly in laboratory rodents by processes that remove the nitroso group to generate the relatively innocuous parent guanidinium compound. The denitrosation of 1,3-dimethyl-2-cyano-1-nitrosoguanidine (CyanoDMNG) me...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(96)00861-1

    authors： Jensen DE,Belka GK,Dworkin C

    更新日期：1997-05-09 00:00:00

  • In vitro drug metabolism and pharmacokinetics of diazepam in cynomolgus monkey hepatocytes during culture for six days.

    abstract：:Diazepam (DZ), N-desmethyl diazepam (NOR) and temazepam (TEM) were used as substrates in drug metabolism studies to characterize the changes in cytochrome P-450 mono-oxygenase pathways in hepatocytes isolated from cynomolgus monkeys, during culture for 6 days. Hepatocytes were incubated with DZ (20 microM), NOR (6 mic...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(89)90547-9

    authors： Seddon T,Lockwood GF,Chenery RJ

    更新日期：1989-08-15 00:00:00

  • Catestatin decreases macrophage function in two mouse models of experimental colitis.

    abstract：:Mucosal inflammation in patients with inflammatory bowel disease (IBD) is characterized by an alteration of prohormone chromogranin A (CgA) production. The recent demonstration of an implication of CgA in collagenous colitis and immune regulation provides a potential link between CgA-derived peptides (catestatin, CTS)...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2014.03.003

    authors： Rabbi MF,Labis B,Metz-Boutigue MH,Bernstein CN,Ghia JE

    更新日期：2014-06-01 00:00:00

  • Inhibition of gastric tumor growth by a novel Hsp90 inhibitor.

    abstract：:Heat shock protein 90 (Hsp90) is a molecular chaperone engaging in multiple cellular signaling by stabilizing oncoproteins (e.g. Akt and c-Raf) in tumor cells. Whereas Hsp90 inhibitors such as 17-AAG exert promising antitumor effects in clinical trials, current efforts focus on developing agents targeting Hsp90 with i...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2013.02.003

    authors： Lu C,Liu D,Jin J,Deokar H,Zhang Y,Buolamwini JK,Yu X,Yan C,Chen X

    更新日期：2013-05-01 00:00:00

  • Similar pyruvate kinase modifications in glioblastoma cells by 7β-hydroxycholesterol and glutamine withdrawal.

    abstract：:Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer. We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells. These ob...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2013.03.012

    authors： de Weille J,Fabre C,Gaven C,Bakalara N

    更新日期：2013-07-01 00:00:00

  • Angiotensin metabolism by cerebral microvascular aminopeptidase A.

    abstract：:Porcine cerebral microvessels were isolated by differential sieving and centrifugation and were characterized by microscopic examination and marker enzyme enrichment (gamma-glutamyltransferase; EC 2.3.2.2). Purified microvessels contained a membrane-bound enzyme immunologically indistinguishable from renal aminopeptid...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(88)90712-5

    authors： Bausback HH,Churchill L,Ward PE

    更新日期：1988-01-15 00:00:00

  • Inhibition of fatty acid biosynthesis by bezafibrate in different rat cells.

    abstract：:Bezafibrate is one of the main drugs used in the treatment of human hyperlipemic diseases. Its action on the biosynthesis of fatty acids has been studied and the following conclusions have been drawn: (1) Lipogenesis from glucose is inhibited in hepatocytes and adipocytes isolated from "refed" rats previously treated ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(89)90095-6

    authors： Villanueva C,Fabregat I,Machado A

    更新日期：1989-08-01 00:00:00

  • Differential expression of renal adenosine A(1) receptors induced by acute renal failure.

    abstract：:The distribution of renal adenosine A(1) receptors was investigated in rats with glycerol- or mercuric chloride (HgCl(2))-induced acute renal failure. Receptors were localised by autoradiography using [(3)H]8-cyclopentyl-1,3-dipropylxanthine ([(3)H]DPCPX), a selective A(1) adenosine receptor antagonist. In saline-inje...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(99)00369-x

    authors： Smith JA,Whitaker EM,Bowmer CJ,Yates MS

    更新日期：2000-03-15 00:00:00

  • Serine residues in the α4 nicotinic acetylcholine receptor subunit regulate surface α4β2* receptor expression and clustering.

    abstract：BACKGROUND AND PURPOSE:Chronic nicotine exposure upregulates α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The goal of this study was to examine the role of three serine residues in the large cytoplasmic loop of the α4 subunit on α4β2* upregulation in neurons. EXPERIMENTAL APPROACH:Serine residues S33...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2018.11.008

    authors： Zambrano CA,Escobar D,Ramos-Santiago T,Bollinger I,Stitzel J

    更新日期：2019-01-01 00:00:00

  • Studies on the mechanism of resistance to mitomycin C and porfiromycin in a human cell strain derived from a cancer-prone individual.

    abstract：:The mechanism of aerobic resistance to the quinone-containing anti-tumour agents mitomycin C (MMC) and porfiromycin (PM) has been investigated using non-transformed human cells. One of the cell strains used (3437T) was derived from an afflicted member of a cancer-prone family. This cell strain had been shown previousl...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(91)90108-h

    authors： Marshall RS,Paterson MC,Rauth AM

    更新日期：1991-05-01 00:00:00

  • Studies on microsomal azoreduction. N,N-dimethyl-4-aminoazobenzene (DAB) and its derivatives.

    abstract：:The azoreduction of N,N-dimethyl-4-aminoazobenzene (DAB) and N-methyl-4-amino-azobenzene (MAB) by rat liver microsomes was investigated. It was shown that measurement of azoreduction of DAB and structurally related azo dyes by the conventional method of substrate disappearance required an anaerobic environment since N...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(85)90343-0

    authors： Levine WG

    更新日期：1985-09-15 00:00:00

  • Effects of 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid on extrahepatic sulfhydryl levels in mice treated with acetaminophen.

    abstract：:The cysteine (Cys) precursor 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA) has been shown to protect against acetaminophen (APAP)-induced hepatic GSH, GSSG, and Cys depletion and hepatic necrosis. The aim of this study was to determine the effects of PTCA on the concentrations of sulfhydryl compounds in extra...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(01)00539-1

    authors： Srinivasan C,Williams WM,Nagasawa HT,Chen TS

    更新日期：2001-04-01 00:00:00

  • Effects of dietary vanadium exposure on levels of regional brain neurotransmitters and their metabolites.

    abstract：:Adult male CD-1 mice were treated with various levels of vanadate in drinking water for 30 days. The levels of catecholamine and indoleamine neurotransmitters and their major metabolites were measured in six different brain regions. Vanadium caused a dose-related decrease in norepinephrine (NE) levels in hypothalamus,...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(86)90220-0

    authors： Sharma RP,Coulombe RA Jr,Srisuchart B

    更新日期：1986-02-01 00:00:00

  • Nrf2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response.

    abstract：:Nuclear factor-E2-related factor 2 (Nrf2) is a master transcription factor in antioxidant response, protecting against oxidative damage and various diseases. Previous studies suggest that Nrf2 is suppressed in fibrotic skin and Nrf2 agonists represent a therapeutic strategy, which is mainly attributed to Nrf2 function...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2020.113846

    authors： Wu R,Zhang H,Zhao M,Li J,Hu Y,Fu J,Pi J,Wang H,Xu Y

    更新日期：2020-04-01 00:00:00