Disease relevance of 2-aminopurine

• The mechanism of isomerization (basepair openings) during transcription initiation by RNA polymerase at the galP1 promoter of Escherichia coli was investigated by 2-aminopurine (2,AP) fluorescence [1].
• We measured the in vivo incorporation of 2-aminopurine into DNA of T4 bacteriophage allelic for gene 43 (DNA polymerase), mutator (L56), 43+, and antimutator (L141) [2].
• In this report we demonstrate that the shut-off of cellular protein synthesis by adenovirus is prevented in cells by treatment with the drug 2-aminopurine [3].
• Detergent-treated lymphocyte nuclei undergoing a high level of EBV DNA synthesis were shown to incorporate the 2-aminopurine analog of dATP into viral DNA [4].
• We find that treatment of mouse hepatoma Hepa-1 cells with 2-aminopurine, an inhibitor of protein kinase activity, inhibits CYP1A1 mRNA induction by TCDD as well as the concomitant increase in CYP1A1 enzyme activity [5].

High impact information on 2-aminopurine

• 2-Aminopurine selectively inhibits the induction of beta-interferon, c-fos, and c-myc gene expression [6].
• When this element, designated 2-APRE, is present, splicing becomes sensitive to inhibition by the PKR inhibitor, 2-aminopurine, or by coexpression of transdominant-negative mutant PKR [7].
• In addition, the inhibition of IL-2-R-induced c-myb expression by 2-aminopurine and enhanced induction of c-myb via the TCR demonstrate that TCR activation and IL-2-R activation lead to induction of c-myb by different mechanisms [8].
• Inhibition of PKR phosphorylation by 2-aminopurine, or deletion of the Pkr gene, led to drastic enhancement of reovirus protein synthesis in untransformed cells [9].
• Here we show that inhibition of an early G1-phase protein kinase pathway by the addition of 2-aminopurine (2-AP) prior to the ODP arrests CHO cells in G1-phase [10].

Chemical compound and disease context of 2-aminopurine

• The Epstein-Barr virus (EBV)-induced intracellular DNA polymerase was assayed in vitro for the ability to utilize the mutagenic nucleotide analog 2-aminopurine deoxyribose triphosphate (d2apTP), incorporating it as the corresponding monophosphate into DNA or poly[d)(A-T)] template [4].
• Ribonucleoside and deoxyribonucleoside triphosphate pools during 2-aminopurine mutagenesis in T4 mutator-, wild type-, and antimutator-infected Escherichia coli [11].
• In this approach, we insert the fluorescent base analogue 2-aminopurine in place of A1492 in an E. coli 16S rRNA A-site model oligonucleotide (EcWT) as well as in a mutant form of this oligomer (A1408G) in which A1408 has been replaced with a guanine [12].
• The frequencies of 2-aminopurine- and 5-bromouracil-induced A:T leads to G:C transitions were compared at nonsense sites throughout the rII region of bacteriophage T4 [13].
• When the Streptococcus pneumoniae TrmD protein was bound to synthetic tRNA(1)(Leu) substituted with 2-aminopurine at positions 36 and 37, fluorescence energy transfer analysis showed that a decrease in 2-aminopurine fluorescence occurs only when AdoMet is present [14].

Biological context of 2-aminopurine

• AB formation is prevented by activation of protein kinase C by phorbol ester or by treatment with the kinase inhibitor 2-aminopurine, without any detectable effect on tyrosine phosphorylation [15].
• 2-aminopurine override of G2 arrest imposed by VM-26 or ICRF-193, which inhibit topoisomerase II (topo II)-dependent DNA decatenation, results in the activation of p34cdc2 kinase and entry into mitosis [16].
• These findings imply that both phorbol esters and 2-aminopurine operate, at least in part, at the level of alternative pathways that may diverge upstream of the MAP kinase and are presumably mediating the early effects of v-Src on the differentiated phenotype [15].
• In addition, the signal transduction cascade that culminates in MAP kinase activation and its nuclear translocation is activated both by v-Src and phorbol ester, and is relatively unaffected by 2-aminopurine [15].
• To determine the basis for this discrepancy in the correlation between carcinogenesis and mutagenesis, the ability of 2-aminopurine to induce somatic mutation and neoplastic transformation concomitantly in the same cellular system was examined [17].

Anatomical context of 2-aminopurine

• The protein kinase inhibitor 2-aminopurine induces checkpoint override and mitotic exit in BHK cells which have been arrested in mitosis by inhibitors of microtubule function (Andreassen, P. R., and R. L. Margolis. 1991. J. Cell Sci. 100:299-310) [18].
• In human and mouse cell lines, expression of exogenous genes was enhanced by treatment with 2-aminopurine (2-AP) [19].
• The PKR inhibitor 2-aminopurine (2-AP) inhibited TNF-alpha/IFN-gamma-induced NF-kappaB nuclear translocation in neuronal derived cells but not in endothelial cells [20].
• 2-Aminopurine induces spindle cell morphology in MM14 myoblasts in the absence of differentiation signals [21].
• When HeLa cells were infected with R2-2A-2 in the presence of 2-aminopurine, a protein kinase inhibitor, much higher virus titers were produced, cleavage of p220 occurred, and host cell protein synthesis was specifically inhibited [22].

Associations of 2-aminopurine with other chemical compounds

• Adenine and 2-aminopurine: paradigms of modern theoretical photochemistry [23].
• Although hamster cells underwent premature mitosis following treatment with caffeine, the protein phosphatase inhibitor okadaic acid, and the protein kinase inhibitors 2-aminopurine and 6-dimethyl-aminopurine, the mouse and human cells examined in this study displayed little or no response to any of these compounds [24].
• GRP78 induction occurs by a pathway that requires protein synthesis and is sensitive to genistein, H7, and 2-aminopurine, whereas gadd gene induction is independent of protein synthesis and is inhibited by H7 and 2-aminopurine only [25].
• Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2alpha phosphorylation, and apoptosis induction by Ad-mda7 [26].
• Increased expression of GRPs after treatment with chemical inducers is sensitive to cycloheximide and the protein kinase inhibitors genistein, 2-aminopurine, and H7, whereas the increase in gadd gene mRNA could be blocked by the protein kinase inhibitors H7 and 2-aminopurine but not by genistein or cycloheximide [25].

Gene context of 2-aminopurine

• Formation of DNA-protein complexes between the Ah receptor and its AhRE target is also inhibited by 2-aminopurine, as determined by gel mobility shift assays [5].
• Specific inhibition of PKR by 2-aminopurine in these FA BM cells attenuates PKR activation and apoptosis induction [27].
• Although CaMKII was not affected by inhibition of PKR with 2-aminopurine, phosphorylation of MKK3/6 and p38 as well as eIF2alpha were significantly reduced [28].
• In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine [29].
• 2-Aminopurine abolishes epidermal growth factor-stimulated phosphorylation of complexed and chromatin-associated forms of a 33 kDa phosphoprotein [30].

Analytical, diagnostic and therapeutic context of 2-aminopurine

• Low-energy circular dichroism of 2-aminopurine dinucleotide as a probe of local conformation of DNA and RNA [31].
• Fluorescence titrations and stopped-flow kinetic analysis of interactions with duplex oligonucleotides containing 2-aminopurine at the target base position indicate that the T250G mutation leads to a more polar but less solvent-accessible position of the flipped out target base [32].
• Stopped-flow fluorometry monitoring the 2-aminopurine fluorescence defined the kinetics of uracil flipping [33].
• The in vitro synthesized TIK protein migrated as a 65 kDa protein on SDS-PAGE when incubated with ATP, but migrated as a 60 kDa protein when incubated with an inhibitor of PKR, 2-aminopurine [34].
• We have previously shown that anisomycin, a protein synthesis inhibitor, and 2-aminopurine, a specific inhibitor of the double stranded-RNA dependent protein kinase, block apoptosis of ganglion cells induced by axotomy, and induce apoptosis of cells in the neuroblastic layer in developing rat retina [35].

References