Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human melanoma provides a model to study malignant transformation and tumor progression. Expression of ras oncogenes in cultured normal human diploid melanocytes has induced a subset of phenotypic traits that are characteristic of malignant melanoma cells, including altered morphology, anchorage independence, induction of class II MHC antigens, up-regulation of the ganglioside GD3, and chromosomal abnormalities. However, other characteristics of melanoma, such as loss of expression of adenosine deaminase-binding protein and tumorigenicity, were not observed. We report here that melanocytes infected with a retrovirus containing the viral Ha-ras oncogene underwent complete transformation, acquiring all phenotypic characteristics of malignant melanomas observed in vivo. Transformation occurred in a sequential manner and was associated with spontaneous chromosomal instability. Cytogenetic analysis of transformed melanocytes indicated that the earliest structural chromosomal abnormalities were isochromosomes 6p and 9q followed by complete loss of chromosome 1p, all common karyotypic abnormalities described in human melanomas. The findings suggest that these chromosome regions which are deleted or relatively deficient may contain genes that are critical for the initiation and progression of the melanoma phenotype.
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PMID:Malignant transformation of human melanocytes: induction of a complete melanoma phenotype and genotype. 143 53

Human melanocytes infected with Ki-MSV or Ha-MSV, but not amphotropic MuLV, undergo a series of transformation-related changes that are characteristic of malignant melanoma. These are (a) expression of Ia antigens, in particular DP, DQ, and DR class II histocompatibility gene products, (b) a transformed morphology and ability to grow in soft agar, and (c) a 5-10-fold increase in the cell surface expression of GD3 ganglioside. However, other characteristics of melanoma, such as independence from specific growth factors and loss of adenosine deaminase binding protein were not observed. We conclude that viral ras oncogenes initiate early transformation events in melanocytes, and that Ia antigen expression is a transformation marker in this system.
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PMID:Class II histocompatibility antigen expression in human melanocytes transformed by Harvey murine sarcoma virus (Ha-MSV) and Kirsten MSV retroviruses. 243 46

The introduction of human p53 with mutation at codon 273 into Rat-1 cells induces changes in the salvage pathway of nucleotide synthesis. In cells expressing the mutant p53 the activities of hypoxanthine phosphoribosyl transferase (HPRT) and thymidide kinase (TK) decrease 3.5- and 2-3-fold, respectively, while the activities of adenosine deaminase and uridine kinase, in contrast, increase correspondingly 2.5- and 1.5-fold. On the other hand, in cells transformed by ras oncogene, which causes dramatical reduction in HPRT activity as well as enhancement of TK function, the expression of exogeneous p53 leads to the opposite effects and causes the reversion of activities of both enzymes to the levels found in parental cells.
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PMID:Human p53, mutated at codon 273, causes distinct effects on nucleotide biosynthesis salvage pathway key enzymes in Rat-1 cells and in their derivatives expressing activated ras oncogene. 833 54

The effects of exogenous human p53 and its various mutants (Ala-141, His-175, His-194, Trp-248, His-273) on two key enzymes of purine uptake, adenosine deaminase (AD) and hypoxanthine phosphoribosyl transferase (HPRT), has been studied in Rat 1 immortalized fibroblasts and their sublines transformed by N-RAS or v-mos oncogenes. Introduction into Rat1 cells of both wild type (wt) and mutant p53 produced a 2- to 7.5-fold increase in the AD activity, p53 mutants having a stronger effect than p53wt. In contrast, the HPRT activity decreased 8- to 10-fold in cells containing exogenous p53wt, while p53 mutants partly lost their ability to inhibit HPRT. Transformation of Rat1 by ras or mos oncogenes was also accompanied by an increase in the AD activity (4-5-fold and 1.5-2-fold, respectively) as well as by suppression of HPRT (20-fold and 2-fold, respectively). However, simultaneous expression of exogenous p53 and ras or p53 and mos produced opposite effects, i.e., a dramatic decrease in the AD activity and complete (p53wt, His-273) or partial (His-175, Trp-248) restoration of the HPRT activity. Possible functional significance and mechanisms of AD and HPRT regulation by p53 as well as the role of modifications of activity of nucleotide synthesis enzymes in the cooperative effect of predominant oncogenes and mutant p53 oncogenes in tumour transformation are discussed.
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PMID:[Opposite effect of p53 on nucleotide metabolizing enzyme activity in Rat1 cells and their sublines, transformed by N-RAS or v-mos oncogenes]. 859 Jul 59

We examined the possible implication of ras in the regulation of the activity of several metabolic enzymes by employing an inducible H-ras expression system (RFLSVrasLAP cell line), in which the addition of IPTG decreases the levels of ras p21 3-fold. We measured the activity of hexokinase (E.C. 2.7.1.1.), glucose phosphate isomerase (E.C. 5.3.1.9), phospho-fructokinase (E.C. 2.7.1.11), aldolase (E.C. 4.1.2.13), phosphoglycerate kinase (E.C. 2.7.2.3), enolase (E.C. 4.2.1.11), pyruvate kinase (E.C. 2.7.1.40), lactate dehydrogenase (E.C. 1.1.1.27), adenosine deaminase (E.C. 3.5.4.4) and purine nucleoside phosphorylase (E.C. 2.4.2.1) from cells grown in the presence and absence of IPTG. We found that the addition of IPTG to RFLSVrasLAP cells led to lower activity of phosphoglycerate kinase (p=0.004), enolase (p=0.027) and pyruvate kinase (p=0.031). Enolase mRNA levels were found to be increased in cells overexpressing either the normal or mutant H-ras. The total rate of glycolysis was not affected by H-ras expression indicating that the implication of H-ras in the activity of phosphoglycerate kinase, enolase and pyruvate kinase may be associated with glycolysis-independent functions of these enzymes. Adenosine deaminase activity was found to increase after IPTG addition (P=0.009), indicating also a possible role for H-ras in the control of the purine nucleotide salvage pathway.
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PMID:T24 h-ras gene-expression increases the activity of phosphoglycerate kinase, enolase and pyruvate-kinase and decreases the activity of adenosine-deaminase in fibroblast cells. 2160 14

Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.
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PMID:The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication. 2385 84