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. 1987 Mar;79(3):1001–1005. doi: 10.1172/JCI112866

Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis.

E G Chottiner, H J Cloft, A P Tartaglia, B S Mitchell
PMCID: PMC424261  PMID: 3029177

Abstract

We have investigated the molecular basis of the marked elevation in erythrocyte adenosine deaminase (ADA) activity in a kindred with hereditary hemolytic anemia. Red cell ADA-specific activity was verified to be 70- to 100-fold normal levels. Western blots demonstrated a corresponding increase in erythrocyte ADA-specific immunoreactive protein. Analysis of genomic DNA revealed no evidence for amplification or major structural changes in the ADA gene. ADA-specific messenger RNA (mRNA) from proband reticulocytes was comparable in size and amount to mRNA from control reticulocytes. Translation of proband poly A+ reticulocyte mRNA in a rabbit reticulocyte lysate system and immunoprecipitation of 35S-labeled protein products with anti-ADA antibody yielded a band of approximately 42,000 apparent mol wt that was absent in translation products from control reticulocyte mRNAs. These data suggest that the increased ADA activity in red cells in this disorder results from the increased translation of an aberrant ADA mRNA.

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Selected References

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  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Daddona P. E., Kelley W. N. Human adenosine deaminase. Purification and subunit structure. J Biol Chem. 1977 Jan 10;252(1):110–115. [PubMed] [Google Scholar]
  4. Daddona P. E., Shewach D. S., Kelley W. N., Argos P., Markham A. F., Orkin S. H. Human adenosine deaminase. cDNA and complete primary amino acid sequence. J Biol Chem. 1984 Oct 10;259(19):12101–12106. [PubMed] [Google Scholar]
  5. Darveau A., Pelletier J., Sonenberg N. Differential efficiencies of in vitro translation of mouse c-myc transcripts differing in the 5' untranslated region. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2315–2319. doi: 10.1073/pnas.82.8.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fujii H., Miwa S., Tani K., Fujinami N., Asano H. Overproduction of structurally normal enzyme in man: hereditary haemolytic anaemia with increased red cell adenosine deaminase activity. Br J Haematol. 1982 Jul;51(3):427–430. doi: 10.1111/j.1365-2141.1982.tb02798.x. [DOI] [PubMed] [Google Scholar]
  7. Giblett E. R., Anderson J. E., Cohen F., Pollara B., Meuwissen H. J. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067–1069. doi: 10.1016/s0140-6736(72)92345-8. [DOI] [PubMed] [Google Scholar]
  8. Hirschhorn R., Roegner V., Jenkins T., Seaman C., Piomelli S., Borkowsky W. Erythrocyte adenosine deaminase deficiency without immunodeficiency. Evidence for an unstable mutant enzyme. J Clin Invest. 1979 Oct;64(4):1130–1139. doi: 10.1172/JCI109552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kessler S. W. Use of protein A-bearing staphylococci for the immunoprecipitation and isolation of antigens from cells. Methods Enzymol. 1981;73(Pt B):442–459. doi: 10.1016/0076-6879(81)73084-2. [DOI] [PubMed] [Google Scholar]
  10. Knoller S., Kaempfer R. Isolation of a heme-controlled inhibitor of translation that blocks the interaction between messenger rna and eukaryotic initiation factor 2. Biochemistry. 1984 May 22;23(11):2462–2469. doi: 10.1021/bi00306a022. [DOI] [PubMed] [Google Scholar]
  11. Kozak M. Point mutations close to the AUG initiator codon affect the efficiency of translation of rat preproinsulin in vivo. Nature. 1984 Mar 15;308(5956):241–246. doi: 10.1038/308241a0. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Mitchell B. S., Edwards N. L., Koller C. A. Deoxyribonucleoside triphosphate accumulation by leukemic cells. Blood. 1983 Aug;62(2):419–424. [PubMed] [Google Scholar]
  14. Mitchell B. S., Mejias E., Daddona P. E., Kelley W. N. Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5011–5014. doi: 10.1073/pnas.75.10.5011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miwa S., Fujii H., Matsumoto N., Nakatsuji T., Oda S., Asano H., Asano S. A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan. Am J Hematol. 1978;5(2):107–115. doi: 10.1002/ajh.2830050205. [DOI] [PubMed] [Google Scholar]
  16. Paglia D. E., Valentine W. N., Tartaglia A. P., Gilsanz F., Sparkes R. S. Control of red blood cell adenine nucleotide metabolism studies of adenosine deaminase. Prog Clin Biol Res. 1978;21:319–338. [PubMed] [Google Scholar]
  17. Pelletier J., Sonenberg N. Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency. Cell. 1985 Mar;40(3):515–526. doi: 10.1016/0092-8674(85)90200-4. [DOI] [PubMed] [Google Scholar]
  18. Pérignon J. L., Hamet M., Buc H. A., Cartier P. H., Derycke M. Biochemical study of a case of hemolytic anemia with increased (85 fold) red cell adenosine deaminase. Clin Chim Acta. 1982 Sep 15;124(2):205–212. doi: 10.1016/0009-8981(82)90388-6. [DOI] [PubMed] [Google Scholar]
  19. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Valentine W. N., Paglia D. E., Tartaglia A. P., Gilsanz F. Hereditary hemolytic anemia with increased red cell adenosine deaminase (45- to 70-fold) and decreased adenosine triphosphate. Science. 1977 Feb 25;195(4280):783–785. doi: 10.1126/science.836588. [DOI] [PubMed] [Google Scholar]
  21. Valerio D., Duyvesteyn M. G., Dekker B. M., Weeda G., Berkvens T. M., van der Voorn L., van Ormondt H., van der Eb A. J. Adenosine deaminase: characterization and expression of a gene with a remarkable promoter. EMBO J. 1985 Feb;4(2):437–443. doi: 10.1002/j.1460-2075.1985.tb03648.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wiginton D. A., Adrian G. S., Hutton J. J. Sequence of human adenosine deaminase cDNA including the coding region and a small intron. Nucleic Acids Res. 1984 Mar 12;12(5):2439–2446. doi: 10.1093/nar/12.5.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wilson J. M., Baugher B. W., Mattes P. M., Daddona P. E., Kelley W. N. Human hypoxanthine-guanine phosphoribosyltransferase. Demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme. J Clin Invest. 1982 Mar;69(3):706–715. doi: 10.1172/JCI110499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wilson J. T., Wilson L. B., deRiel J. K., Villa-komaroff L., Efstratiadis A., Forget B. G., Weissman S. M. Insertion of synthetic copies of human globin genes into bacterial plasmids. Nucleic Acids Res. 1978 Feb;5(2):563–581. doi: 10.1093/nar/5.2.563. [DOI] [PMC free article] [PubMed] [Google Scholar]

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