Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphology, fine structure, karyology and growth of intrathymus pre-T-cell cultures (TC.SC-1/1.1 and TC.SC-1/2.0) were studied both in vitro and in vivo. The cultures were induced by injecting to mice a supernatant enriched with interleukin 2. The results obtained confirm the malignant transformation of cells of the lines obtained and the involvement of endogenic lymphotropic viruses in this process. The lines obtained are defective in hypoxanthine phosphoribosyltransferase. This property may serve as a basis for their use in hybridoma technology.
Tsitologiia 1987 Sep
PMID:[Lines of transformed mouse thymus cells. II. Cell morphology, karyology, ultrastructure and growth in vitro and in vivo]. 350 22

Simple methods for the detection of hypoxanthine-guanine phosphoribosyltransferase and/or adenine phosphoribosyltransferase deficiencies using dried filter paper blood spots were studied. Enzyme activities in the eluate from dried filter paper blood spots stored for 4 weeks at room conditions were shown to be quite stable. Autoradiographs prepared from dried filter paper blood spots and DE-81 papers soaked with enzyme reaction mixtures containing 14C-hypoxanthine and/or 14C-adenine showed sharp radioactive spots in normal subjects. No activity was evident in the cases of the Lesch-Nyhan syndrome and/or adenine phosphoribosyltransferase deficiency. The methods seem to be suitable for screening.
Ann Clin Biochem 1986 Sep
PMID:Simple screening methods for hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase deficiencies using dried blood spots on filter paper. 376 88

Most drugs available for cancer chemotherapy exert their effects through cytodestruction. Although significant advances have been attained with these cytotoxic agents in several malignant diseases, response is often accompanied by significant morbidity and many common malignant tumours respond poorly to existing cytotoxic therapy. Development of chemotherapeutic agents with non-cytodestructive actions appears desirable. Considerable evidence exists which indicates that (a) the malignant state is not irreversible and represents a disease of altered maturation, and (b) some experimental tumour systems can be induced by chemical agents to differentiate to mature end-stage cells with no proliferative potential. Thus, it is conceivable that therapeutic agents can be developed which convert cancer cells to benign forms. To study the phenomenon of blocked maturation, squamous carcinoma SqCC/Y1 cells were employed in culture. Using this system it was possible to demonstrate that physiological levels of retinoic acid and epidermal growth factor were capable of preventing the differentiation of these malignant keratinocytes into a mature tissue-like structure. The terminal differentiation caused by certain antineoplastic agents was investigated in HL-60 promyelocytic leukaemia cells to provide information on the mechanism by which chemotherapeutic agents induce cells to by-pass a maturation block. The anthracyclines aclacinomycin A and marcellomycin were potent inhibitors of N-glycosidically linked glycoprotein biosynthesis and transferrin receptor activity, and active inducers of maturation; temporal studies suggested that the biochemical effects were associated with the differentiation process. 6-Thioguanine produced cytotoxicity in parental cells by forming analog nucleotide. In hypoxanthine-guanine phosphoribosyltransferase negative HL-60 cells the 6-thiopurine initiated maturation; this action was due to the free base (and possibly the deoxyribonucleoside), a finding which separated termination of proliferation due to cytotoxicity from that caused by maturation.
Br J Cancer 1985 Sep
PMID:The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach. 389 54

Murine stocks with wild-derived hypoxanthine phosphoribosyltransferase (HPRT) A alleles (Hprt a) have erythrocyte HPRT activity levels that are approximately 25-fold (Mus musculus castaneus) and 70-fold (Mus spretus) higher than those of laboratory strains of mice with the common Hprt b allele (Mus musculus: C3H/HeHa or C57B1/6). Since the purified HPRT A and B enzymes have substantially similar maximal specific activities (64 and 46 units/mg of protein, respectively), we infer that these HPRT activity levels closely approximate the relative levels of HPRT protein in these cells. Red blood cells of HPRT A and B mice have similar levels of adenine phosphoribosyltransferase activity (APRT; EC 2.4.2.7) and reticulocyte percentages, which suggests that the elevated levels of HPRT in erythrocytes of HPRT A mice are not secondary consequences of abnormal erythroid cell development. The HPRT activity levels in reticulocytes of HPRT B mice are approximately 35-fold higher than the levels in their erythrocytes and approach the HPRT activity levels in reticulocytes of HPRT A mice. Thus, the marked differences in the levels of HPRT protein in erythrocytes of HPRT A and B mice result from differences in the extent to which the HPRT A and B proteins are retained as reticulocytes mature to erythrocytes. The substantial and preferential loss of HPRT B activity from reticulocytes is paralleled by an equivalent loss of HPRT immunoreactive protein (i.e., CRM) from that cell, and we infer that the HPRT B protein is degraded or extruded as reticulocytes mature to erythrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochemistry 1985 Sep 10
PMID:Elevated levels of erythrocyte hypoxanthine phosphoribosyltransferase associated with allelic variation of murine Hprt. 407 78

Deficient hypoxanthine-guanine phosphoribosyl transferase (HGPRT; EC 2.4.2.8) enzymes from erythrocytes of patients with hyperuricemia and with the Lesch-Nyhan syndrome migrate 15% faster in polyacrylamide gel disc electrophoresis than the normal enzyme. A half-sister of two males with partial deficiency, who had 34% of normal HGPRT activity in her erythrocytes, yielded profiles containing two distinct zones of activity; one corresponded to the enzyme found in normal individuals and one to the variant of her half-brothers. However, in her profile her variant enzyme showed notably greater activity than that observed in her half-brothers. This increase was due to an activation of the variant by normal enzyme. Electrophoresis of mixtures of normal enzyme with partially deficient enzymes from patients with hyperuricemia and with the Lesch-Nyhan syndrome also led to activation of deficient HGPRT variants by normal enzymes. Deficient variants were also activated by normal enzyme on filtration through Sephadex G-25. Experiments in which deficient variant enzymes were activated with purified normal enzyme labeled with (125)I indicated that deficient enzymes incorporate components of the normal enzyme. No such activation of deficient enzymes was ever obtained when mixtures of deficient and normal enzymes were put together in a test tube.
Proc Natl Acad Sci U S A 1972 Sep
PMID:Activation of variants of hypoxanthine-guanine phosphoribosyl transferase by the normal enzyme. 434 98

We have previously described a 14-yr-old boy with hyperuricemia, renal failure, and accelerated purine production resistant in vivo and in vitro to purine analogs. This patient demonstrated normal red cell hypoxanthine-guanine phosphoribosyltransferase (HPRT) heat stability, electrophoresis at high pH, and activity at standard substrate levels. In the present report an abnormal HPRT enzyme was demonstrated by enzyme kinetic study with phosphoribosylpyrophosphate (PRPP) as the variable substrate and inhibitory studies with sodium fluoride. Apparently normal HPRT activity in a patient with hyperuricemia and gout does not exclude a functionally significant HPRT mutation.
J Clin Invest 1973 Sep
PMID:Hypoxanthine-guanine phosphoribosyltransferase variant associated with accelerated purine synthesis. 435 74

Fusion of hypoxanthine phosphoribosyltransferase (HPRT)(-) rat hepatoma cells with HPRT(+) human fibroblasts yielded hybrid clones that grew in HAT selective medium and contained all the rat chromosomes and one to nine human chromosomes. Among the retained chromosomes was the human X chromosome. In all clones backselected in medium containing 8-azaguanine, human X chromosome was absent. Electrophoretic analysis revealed that, without exception, hybrid clones growing in HAT medium had an active HPRT enzyme, either human or rat, or both. When these clones were backselected in 8-azaguanine, they did not show HPRT enzyme activity. Hybrids that contained the human X chromosome also had human glucose-6-phosphate dehydrogenase. The observed reexpression of rat HPRT in hybrid cells derived from HPRT(-) rat cells suggests that a genetic factor from the human cell determined the expression of the rat structural gene for HPRT.
Proc Natl Acad Sci U S A 1973 Sep
PMID:Reexpression of the rat hypoxanthine phosphoribosyltransferase gene in rat-human hybrids. 435 57

1. The purine bases adenine, hypoxanthine and guanine were rapidly incorporated into the nucleotide fraction of Ehrlich ascites-tumour cells in vivo. 2. The reaction of 5'-phosphoribosyl pyrophosphate with adenine phosphoribosyltransferase from ascites-tumour cells (K(m) 6.5-11.9mum) was competitively inhibited by AMP, ADP, ATP and GMP (K(i) 7.5, 21.9, 395 and 118mum respectively). Similarly the reactions of 5'-phosphoribosyl pyrophosphate with both hypoxanthine phosphoribosyltransferase and guanine phosphoribosyltransferase (K(m) 18.4-31 and 37.6-44.2mum respectively) were competitively inhibited by IMP (K(i) 52 and 63.5mum) and by GMP (K(i) 36.5 and 5.9mum). 3. The nucleotides tested as inhibitors did not appreciably compete with the purine bases in the phosphoribosyltransferase reactions. 4. It was postulated that the purine phosphoribosyltransferases of Ehrlich ascites-tumour cells may be effectively separated from the adenine nucleotide pool of these cells.
Biochem J 1966 Sep
PMID:Inhibition of purine phosphoribosyltransferases from Ehrlich ascites-tumour cells by purine nucleotides. 596 81

A growth hormone minigene carrying its natural promoter (237 nucleotides of chromosomal DNA) was stably propagated in a murine retrovirus containing hypoxanthine-guanine phosphoribosyltransferase as a selectable marker. Glucocorticoid and thyroid hormone inducibility was transferred with the growth hormone gene. Recombinant virus with titers of 10(6) per milliliter was recovered. This demonstration that retroviruses can be used to transfer a nonselectable gene under its own regulatory control enlarges the scope of retroviral vectors as potent tools for gene transfer.
Science 1984 Sep 07
PMID:Infectious and selectable retrovirus containing an inducible rat growth hormone minigene. 608 40

Comparative Southern hybridization of cDNA probes to DNA from cells carrying either one or four X chromosomes has been used to distinguish sequences derived from the functional locus for hypoxanthine-guanine phosphoribosyltransferase (HPRT) on the X chromosome from four independent HPRT-like autosomal sequences in the human genome. Subfragments of cDNA were then used to orient fragments from the HPRT locus with respect to the mRNA sequence. The chromosomal origin of each of the autosomal sequences was determined by Southern analysis using DNA from a panel of human-Chinese hamster somatic cell hybrids. Two of the HPRT-like sequences were localized to chromosome 11, the third to chromosome 3, and the fourth to the region between p13 and q11 on chromosome 5. Three of these four autosomal sequences were isolated from genomic recombinant libraries and subcloned fragments from each were used as probes to study restriction fragment length polymorphisms (RFLP) at these loci. A RFLP for MspI was found at the HPRT-like locus on chromosome 5 with a 1.3-kb major allele (frequency = 0.8) and a 3.6-kb minor allele (frequency = 0.2).
Somat Cell Mol Genet 1984 Sep
PMID:Organization of the HPRT gene and related sequences in the human genome. 608 58


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