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PMID: 3006058 Published · ppublish English Journal Article

Protein kinase C phosphorylates topoisomerase II: topoisomerase activation and its possible role in phorbol ester-induced differentiation of HL-60 cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 6 ·1986-03-00 ·Pages 1603-7

Sahyoun N, Wolf M, Besterman J, Hsieh T, Sander M, LeVine H, Chang KJ, Cuatrecasas P

Abstract

DNA topoisomerase II from Drosophila was phosphorylated effectively by protein kinase C. With a Km of about 100 nM, the reaction was rapid, occurring at 4 degrees C as well as at 30 degrees C and requiring as little as 0.6 ng of the protein kinase per 170 ng of topoisomerase. About 0.85 mol of phosphate could be incorporated per mol of topoisomerase II, with phosphoserine as the only phospho amino acid produced. The reaction was dependent on Ca2+ and phosphatidylserine and was stimulated by phorbol esters. Calmodulin-dependent protein kinase II, but not cyclic AMP-dependent protein kinase, was also able to phosphorylate the topoisomerase. Phosphorylation of topoisomerase II by protein kinase C resulted in appreciable activation of the topoisomerase, suggesting that it may represent a possible target for the regulation of nuclear events by protein kinase C. This possibility is supported by the finding that the phorbol ester-induced differentiation of HL-60 cells was blocked by the topoisomerase II inhibitors novobiocin and 4'-(9-acridinylamino)methanesulfon-m-anisidide(m-AMSA), but not by the inactive analog o-AMSA.

MeSH Terms
Aminoacridines/pharmacology Amsacrine Animals Cell Differentiation/drug effects Cell Line DNA Topoisomerases, Type II/metabolism Drosophila melanogaster/enzymology Enzyme Activation Kinetics Leukemia, Myeloid, Acute/pathology Male Novobiocin/pharmacology Phorbol Esters/pharmacology Phosphorylation Phosphoserine/biosynthesis Protein Kinase C/metabolism Protein Kinases/metabolism Rats Rats, Inbred Strains Topoisomerase II Inhibitors
Chemicals
Aminoacridines Phorbol Esters Topoisomerase II Inhibitors Amsacrine Phosphoserine Novobiocin 4'-(9-acridinylamino)methanesulfon-o-anisidide Protein Kinases Protein Kinase C DNA Topoisomerases, Type II
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Sahyoun N
Wolf M
Besterman J
Hsieh T
Sander M
LeVine H
Chang K J
Cuatrecasas P
References (50)
50 references, click to expand
  1. DNA topoisomerase II is required at the time of mitosis in yeast.
    Cell. 1985 Jun;41(2):553-63 PMID: 2985283
  2. Novel partitioning of DNA cleavage sites for Drosophila topoisomerase II.
    Cell. 1985 Apr;40(4):933-41 PMID: 2985270
  3. Tumor promoters and cell transformation.
    Pharmacol Ther. 1984;26(1):89-145 PMID: 6398446
  4. In vivo mapping of DNA topoisomerase II-specific cleavage sites on SV40 chromatin.
    Cell. 1985 May;41(1):127-32 PMID: 2986841
  5. Phosphorylation of DNA topoisomerase II by casein kinase II: modulation of eukaryotic topoisomerase II activity in vitro.
    Proc Natl Acad Sci U S A. 1985 May;82(10):3164-8 PMID: 2987912
  6. In situ localization of DNA topoisomerase II, a major polypeptide component of the Drosophila nuclear matrix fraction.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4142-6 PMID: 2987966
  7. Novobiocin blocks the Drosophila heat shock response.
    J Mol Biol. 1985 May 5;183(1):13-29 PMID: 2989538
  8. DNA topoisomerases.
    Annu Rev Biochem. 1985;54:665-97 PMID: 2992360
  9. The phosphoform of the regulatory subunit RII of cyclic AMP-dependent protein kinase possesses intrinsic topoisomerase activity.
    Cell. 1985 Sep;42(2):429-37 PMID: 2411419
  10. Interaction of protein kinase C with membranes is regulated by Ca2+, phorbol esters, and ATP.
    J Biol Chem. 1985 Dec 15;260(29):15718-22 PMID: 4066694
  11. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  12. Stimulation by cyclic adenosine monophosphate of plasmid deoxyribonucleic acid replication and catabolite repression of the plasmid deoxyribonucleic acid-protein relaxation complex.
    J Bacteriol. 1973 May;114(2):577-91 PMID: 4350343
  13. Induction of the polyamine-biosynthetic enzymes in mouse epidermis by tumor-promoting agents.
    Cancer Res. 1975 Jul;35(7):1662-70 PMID: 48421
  14. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  15. A possible naturally occurring tumor promoter, teleocidin B from Streptomyces.
    Biochem Biophys Res Commun. 1979 Oct 12;90(3):976-83 PMID: 292437
  16. DNA gyrase and the supercoiling of DNA.
    Science. 1980 Feb 29;207(4434):953-60 PMID: 6243420
  17. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311-5 PMID: 6246487
  18. ATP-dependent DNA topoisonmerase from D. melanogaster reversibly catenates duplex DNA rings.
    Cell. 1980 Aug;21(1):115-25 PMID: 6250707
  19. DNA topoisomerases.
    Annu Rev Biochem. 1981;50:879-910 PMID: 6267993
  20. Novel topologically knotted DNA from bacteriophage P4 capsids: studies with DNA topoisomerases.
    Nucleic Acids Res. 1981 Aug 25;9(16):3979-89 PMID: 6272191
  21. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.
    J Biol Chem. 1982 Jul 10;257(13):7847-51 PMID: 7085651
  22. Phosphorylation of purified Novikoff hepatoma topoisomerase I.
    Biochem Biophys Res Commun. 1983 Mar 29;111(3):897-905 PMID: 6301489
  23. Double strand DNA cleavage by type II DNA topoisomerase from Drosophila melanogaster.
    J Biol Chem. 1983 Jul 10;258(13):8421-8 PMID: 6305984
  24. DNA topoisomerase II from Drosophila melanogaster. Purification and physical characterization.
    J Biol Chem. 1983 Aug 10;258(15):9530-5 PMID: 6308010
  25. DNA topoisomerase II from Drosophila melanogaster. Relaxation of supercoiled DNA.
    J Biol Chem. 1983 Aug 10;258(15):9536-43 PMID: 6308011
  26. Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters.
    J Biol Chem. 1983 Oct 10;258(19):11442-5 PMID: 6311812
  27. Purification and properties of type II DNA topoisomerase from embryos of Drosophila melanogaster.
    Methods Enzymol. 1983;100:161-70 PMID: 6312257
  28. Phorbol esters stimulate the phosphorylation of receptors for insulin and somatomedin C.
    Proc Natl Acad Sci U S A. 1983 Oct;80(20):6211-3 PMID: 6312447
  29. Tumor promoter TPA increases initiation of replication on DNA injected into xenopus eggs.
    Cell. 1983 Nov;35(1):63-9 PMID: 6226366
  30. Epidermal growth factor and potent phorbol tumor promoters induce epidermal growth factor receptor phosphorylation in a similar but distinctively different manner in human epidermoid carcinoma A431 cells.
    J Biol Chem. 1984 Feb 25;259(4):2559-67 PMID: 6321474
  31. Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide.
    Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361-5 PMID: 6324188
  32. The role of protein kinase C in cell surface signal transduction and tumour promotion.
    Nature. 1984 Apr 19-25;308(5961):693-8 PMID: 6232463
  33. Association of phorbol ester-induced hyperphosphorylation and reversible regulation of transferrin membrane receptors in HL60 cells.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):2016-20 PMID: 6326098
  34. Continuous suppression of globin gene expression and differentiation of Friend erythroleukemia cells by phorbol 12-myristate 13-acetate (PMA) despite the loss of PMA binding sites by down regulation.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):2075-9 PMID: 6326103
  35. DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication.
    Proc Natl Acad Sci U S A. 1984 May;81(9):2616-20 PMID: 6326134
  36. Ca2+/calmodulin-dependent protein kinases from the neuronal nuclear matrix and post-synaptic density are structurally related.
    Proc Natl Acad Sci U S A. 1984 Jul;81(14):4311-5 PMID: 6589595
  37. Turnover of inositol phospholipids and signal transduction.
    Science. 1984 Sep 21;225(4668):1365-70 PMID: 6147898
  38. Induction of expression and phosphorylation of the human interleukin 2 receptor by a phorbol diester.
    J Biol Chem. 1984 Oct 10;259(19):11706-12 PMID: 6237101
  39. A protein kinase activity tightly associated with Drosophila type II DNA topoisomerase.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):6938-42 PMID: 6095262
  40. Torsional stress promotes the DNAase I sensitivity of active genes.
    Cell. 1984 Dec;39(3 Pt 2):469-78 PMID: 6096006
  41. Regulation of glycophorin gene expression by a tumor-promoting phorbol ester in human leukemic K562 cells.
    J Biol Chem. 1985 Jan 10;260(1):640-5 PMID: 3855301
  42. Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma.
    J Biol Chem. 1985 Jan 10;260(1):98-104 PMID: 3855302
  43. Virus- and cell-encoded tyrosine protein kinases inactivate DNA topoisomerases in vitro.
    Nature. 1984 Dec 20-1985 Jan 2;312(5996):785-6 PMID: 6096721
  44. Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation.
    Cell. 1985 Jan;40(1):209-17 PMID: 3881183
  45. Amiloride inhibits phorbol ester-stimulated Na+/H+ exchange and protein kinase C. An amiloride analog selectively inhibits Na+/H+ exchange.
    J Biol Chem. 1985 Jan 25;260(2):1155-9 PMID: 2981834
  46. Cytoskeletal calmodulin-dependent protein kinase. Characterization, solubilization, and purification from rat brain.
    J Biol Chem. 1985 Jan 25;260(2):1230-7 PMID: 4038501
  47. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester.
    Nature. 1985 Jan 24-30;313(6000):318-20 PMID: 3918270
  48. Induction of cytoskeletal vimentin and actin gene expression by a tumor-promoting phorbol ester in the human leukemic cell line K562.
    J Biol Chem. 1985 Mar 25;260(6):3868-74 PMID: 3838316
  49. Transcriptional modulation of human T-cell growth factor gene by phorbol ester and interleukin 1.
    Biochemistry. 1984 Dec 18;23(26):6685-90 PMID: 6335665
  50. Localization of topoisomerase II in mitotic chromosomes.
    J Cell Biol. 1985 May;100(5):1716-25 PMID: 2985626
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.6.1603
Published
1986-03-00
Pages
1603-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323131
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.83.6.1603 PMC Full Text View journal details
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