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. 1991 Dec;10(13):4311–4320. doi: 10.1002/j.1460-2075.1991.tb05009.x

Both cyclin A delta 60 and B delta 97 are stable and arrest cells in M-phase, but only cyclin B delta 97 turns on cyclin destruction.

F C Luca 1, E K Shibuya 1, C E Dohrmann 1, J V Ruderman 1
PMCID: PMC453184  PMID: 1836759

Abstract

Previous work has established that destruction of cyclin B is necessary for exit from mitosis and entry into the next interphase. Sea urchin cyclin B lacking an N-terminal domain is stable, permanently activates cdc2 kinase, resulting in mitotic arrest, and permanently activates the destruction pathway acting on full length cyclin B. Here we have compared the properties of clam cyclins A and B lacking related N-terminal domains. Both cyclin A delta 60 and B delta 97 bind to cdc2 kinase, keep it hyperactivated and block the completion of mitosis. By adding purified delta cyclin proteins to a cell-free system at different cell cycle times, we find that when the cell-free system reaches the cyclin destruction point in the presence of either A delta 60 or B delta 97, the cyclin destruction pathway acting on full length cyclins fails to be turned off. However, the two cyclins differ dramatically in their ability to turn on cyclin destruction. When added to emetine-arrested interphase lysates devoid of endogenous cyclins, only cyclin B delta 97 activates the cyclin destruction system; cyclin A delta 60 does not. This functional difference between the two cyclin types, the first to be described, provides strong support for the idea that the two cyclins have different roles in the cell cycle and suggests that one specialized role of the cyclin B-cdc2 complex is to activate the cyclin destruction pathway and drive cells into interphase of the next cell cycle.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allende C. C., Hinrichs M. V., Santos E., Allende J. E. Oncogenic ras protein induces meiotic maturation of amphibian oocytes in the presence of protein synthesis inhibitors. FEBS Lett. 1988 Jul 18;234(2):426–430. doi: 10.1016/0014-5793(88)80130-3. [DOI] [PubMed] [Google Scholar]
  2. Anderson C. W., Baum P. R., Gesteland R. F. Processing of adenovirus 2-induced proteins. J Virol. 1973 Aug;12(2):241–252. doi: 10.1128/jvi.12.2.241-252.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birchmeier C., Broek D., Wigler M. ras proteins can induce meiosis in Xenopus oocytes. Cell. 1985 Dec;43(3 Pt 2):615–621. doi: 10.1016/0092-8674(85)90233-8. [DOI] [PubMed] [Google Scholar]
  4. Booher R., Beach D. Interaction between cdc13+ and cdc2+ in the control of mitosis in fission yeast; dissociation of the G1 and G2 roles of the cdc2+ protein kinase. EMBO J. 1987 Nov;6(11):3441–3447. doi: 10.1002/j.1460-2075.1987.tb02667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Booher R., Beach D. Involvement of cdc13+ in mitotic control in Schizosaccharomyces pombe: possible interaction of the gene product with microtubules. EMBO J. 1988 Aug;7(8):2321–2327. doi: 10.1002/j.1460-2075.1988.tb03075.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bradford M. M. 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;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  7. Brizuela L., Draetta G., Beach D. p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase. EMBO J. 1987 Nov;6(11):3507–3514. doi: 10.1002/j.1460-2075.1987.tb02676.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. D'Urso G., Marraccino R. L., Marshak D. R., Roberts J. M. Cell cycle control of DNA replication by a homologue from human cells of the p34cdc2 protein kinase. Science. 1990 Nov 9;250(4982):786–791. doi: 10.1126/science.2173140. [DOI] [PubMed] [Google Scholar]
  9. Draetta G., Beach D. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement. Cell. 1988 Jul 1;54(1):17–26. doi: 10.1016/0092-8674(88)90175-4. [DOI] [PubMed] [Google Scholar]
  10. Draetta G., Brizuela L., Potashkin J., Beach D. Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+. Cell. 1987 Jul 17;50(2):319–325. doi: 10.1016/0092-8674(87)90227-3. [DOI] [PubMed] [Google Scholar]
  11. Draetta G., Luca F., Westendorf J., Brizuela L., Ruderman J., Beach D. Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF. Cell. 1989 Mar 10;56(5):829–838. doi: 10.1016/0092-8674(89)90687-9. [DOI] [PubMed] [Google Scholar]
  12. Draetta G., Piwnica-Worms H., Morrison D., Druker B., Roberts T., Beach D. Human cdc2 protein kinase is a major cell-cycle regulated tyrosine kinase substrate. Nature. 1988 Dec 22;336(6201):738–744. doi: 10.1038/336738a0. [DOI] [PubMed] [Google Scholar]
  13. Drury K. C., Schorderet-Slatkine S. Effects of cycloheximide on the "autocatalytic" nature of the maturation promoting factor (MPF) in oocytes of Xenopus laevis. Cell. 1975 Mar;4(3):269–274. doi: 10.1016/0092-8674(75)90175-0. [DOI] [PubMed] [Google Scholar]
  14. Dunphy W. G., Newport J. W. Fission yeast p13 blocks mitotic activation and tyrosine dephosphorylation of the Xenopus cdc2 protein kinase. Cell. 1989 Jul 14;58(1):181–191. doi: 10.1016/0092-8674(89)90414-5. [DOI] [PubMed] [Google Scholar]
  15. Evans T., Rosenthal E. T., Youngblom J., Distel D., Hunt T. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell. 1983 Jun;33(2):389–396. doi: 10.1016/0092-8674(83)90420-8. [DOI] [PubMed] [Google Scholar]
  16. Félix M. A., Labbé J. C., Dorée M., Hunt T., Karsenti E. Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase. Nature. 1990 Jul 26;346(6282):379–382. doi: 10.1038/346379a0. [DOI] [PubMed] [Google Scholar]
  17. Gautier J., Maller J. L. Cyclin B in Xenopus oocytes: implications for the mechanism of pre-MPF activation. EMBO J. 1991 Jan;10(1):177–182. doi: 10.1002/j.1460-2075.1991.tb07934.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gautier J., Minshull J., Lohka M., Glotzer M., Hunt T., Maller J. L. Cyclin is a component of maturation-promoting factor from Xenopus. Cell. 1990 Feb 9;60(3):487–494. doi: 10.1016/0092-8674(90)90599-a. [DOI] [PubMed] [Google Scholar]
  19. Ghiara J. B., Richardson H. E., Sugimoto K., Henze M., Lew D. J., Wittenberg C., Reed S. I. A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis. Cell. 1991 Apr 5;65(1):163–174. doi: 10.1016/0092-8674(91)90417-w. [DOI] [PubMed] [Google Scholar]
  20. Glotzer M., Murray A. W., Kirschner M. W. Cyclin is degraded by the ubiquitin pathway. Nature. 1991 Jan 10;349(6305):132–138. doi: 10.1038/349132a0. [DOI] [PubMed] [Google Scholar]
  21. Gould K. L., Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. doi: 10.1038/342039a0. [DOI] [PubMed] [Google Scholar]
  22. Hagan I., Hayles J., Nurse P. Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis. J Cell Sci. 1988 Dec;91(Pt 4):587–595. doi: 10.1242/jcs.91.4.587. [DOI] [PubMed] [Google Scholar]
  23. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  24. Hershko A., Ganoth D., Pehrson J., Palazzo R. E., Cohen L. H. Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. J Biol Chem. 1991 Sep 5;266(25):16376–16379. [PubMed] [Google Scholar]
  25. Kobayashi H., Minshull J., Ford C., Golsteyn R., Poon R., Hunt T. On the synthesis and destruction of A- and B-type cyclins during oogenesis and meiotic maturation in Xenopus laevis. J Cell Biol. 1991 Aug;114(4):755–765. doi: 10.1083/jcb.114.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kumagai A., Dunphy W. G. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell. 1991 Mar 8;64(5):903–914. doi: 10.1016/0092-8674(91)90315-p. [DOI] [PubMed] [Google Scholar]
  27. Labbe J. C., Picard A., Peaucellier G., Cavadore J. C., Nurse P., Doree M. Purification of MPF from starfish: identification as the H1 histone kinase p34cdc2 and a possible mechanism for its periodic activation. Cell. 1989 Apr 21;57(2):253–263. doi: 10.1016/0092-8674(89)90963-x. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Lehner C. F., O'Farrell P. H. The roles of Drosophila cyclins A and B in mitotic control. Cell. 1990 May 4;61(3):535–547. doi: 10.1016/0092-8674(90)90535-m. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lohka M. J., Hayes M. K., Maller J. L. Purification of maturation-promoting factor, an intracellular regulator of early mitotic events. Proc Natl Acad Sci U S A. 1988 May;85(9):3009–3013. doi: 10.1073/pnas.85.9.3009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lorca T., Fesquet D., Zindy F., Le Bouffant F., Cerruti M., Brechot C., Devauchelle G., Dorée M. An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs. Mol Cell Biol. 1991 Feb;11(2):1171–1175. doi: 10.1128/mcb.11.2.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Luca F. C., Ruderman J. V. Control of programmed cyclin destruction in a cell-free system. J Cell Biol. 1989 Nov;109(5):1895–1909. doi: 10.1083/jcb.109.5.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Maller J. L., Krebs E. G. Regulation of oocyte maturation. Curr Top Cell Regul. 1980;16:271–311. doi: 10.1016/b978-0-12-152816-4.50012-1. [DOI] [PubMed] [Google Scholar]
  34. Meijer L., Arion D., Golsteyn R., Pines J., Brizuela L., Hunt T., Beach D. Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase. EMBO J. 1989 Aug;8(8):2275–2282. doi: 10.1002/j.1460-2075.1989.tb08353.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Minshull J., Golsteyn R., Hill C. S., Hunt T. The A- and B-type cyclin associated cdc2 kinases in Xenopus turn on and off at different times in the cell cycle. EMBO J. 1990 Sep;9(9):2865–2875. doi: 10.1002/j.1460-2075.1990.tb07476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Minshull J., Murray A., Colman A., Hunt T. Xenopus oocyte maturation does not require new cyclin synthesis. J Cell Biol. 1991 Aug;114(4):767–772. doi: 10.1083/jcb.114.4.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Minshull J., Pines J., Golsteyn R., Standart N., Mackie S., Colman A., Blow J., Ruderman J. V., Wu M., Hunt T. The role of cyclin synthesis, modification and destruction in the control of cell division. J Cell Sci Suppl. 1989;12:77–97. doi: 10.1242/jcs.1989.supplement_12.8. [DOI] [PubMed] [Google Scholar]
  38. Morla A. O., Draetta G., Beach D., Wang J. Y. Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis. Cell. 1989 Jul 14;58(1):193–203. doi: 10.1016/0092-8674(89)90415-7. [DOI] [PubMed] [Google Scholar]
  39. Murray A. W., Kirschner M. W. Cyclin synthesis drives the early embryonic cell cycle. Nature. 1989 May 25;339(6222):275–280. doi: 10.1038/339275a0. [DOI] [PubMed] [Google Scholar]
  40. Murray A. W., Solomon M. J., Kirschner M. W. The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. Nature. 1989 May 25;339(6222):280–286. doi: 10.1038/339280a0. [DOI] [PubMed] [Google Scholar]
  41. Parker L. L., Atherton-Fessler S., Lee M. S., Ogg S., Falk J. L., Swenson K. I., Piwnica-Worms H. Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner. EMBO J. 1991 May;10(5):1255–1263. doi: 10.1002/j.1460-2075.1991.tb08067.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Pines J., Hunt T. Molecular cloning and characterization of the mRNA for cyclin from sea urchin eggs. EMBO J. 1987 Oct;6(10):2987–2995. doi: 10.1002/j.1460-2075.1987.tb02604.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Pines J., Hunter T. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2. Cell. 1989 Sep 8;58(5):833–846. doi: 10.1016/0092-8674(89)90936-7. [DOI] [PubMed] [Google Scholar]
  44. Pondaven P., Meijer L., Beach D. Activation of M-phase-specific histone H1 kinase by modification of the phosphorylation of its p34cdc2 and cyclin components. Genes Dev. 1990 Jan;4(1):9–17. doi: 10.1101/gad.4.1.9. [DOI] [PubMed] [Google Scholar]
  45. Roy L. M., Swenson K. I., Walker D. H., Gabrielli B. G., Li R. S., Piwnica-Worms H., Maller J. L. Activation of p34cdc2 kinase by cyclin A. J Cell Biol. 1991 May;113(3):507–514. doi: 10.1083/jcb.113.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shibuya E. K., Masui Y. Stabilization and enhancement of primary cytostatic factor (CSF) by ATP and NaF in amphibian egg cytosols. Dev Biol. 1988 Sep;129(1):253–264. doi: 10.1016/0012-1606(88)90179-0. [DOI] [PubMed] [Google Scholar]
  47. Solomon M. J., Glotzer M., Lee T. H., Philippe M., Kirschner M. W. Cyclin activation of p34cdc2. Cell. 1990 Nov 30;63(5):1013–1024. doi: 10.1016/0092-8674(90)90504-8. [DOI] [PubMed] [Google Scholar]
  48. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  49. Swenson K. I., Farrell K. M., Ruderman J. V. The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes. Cell. 1986 Dec 26;47(6):861–870. doi: 10.1016/0092-8674(86)90801-9. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Wasserman W. J., Masui Y. Initiation of meiotic maturation in Xenopus laevis oocytes by the combination of divalent cations and ionophore A23187. J Exp Zool. 1975 Sep;193(3):369–375. doi: 10.1002/jez.1401930313. [DOI] [PubMed] [Google Scholar]
  52. Westendorf J. M., Swenson K. I., Ruderman J. V. The role of cyclin B in meiosis I. J Cell Biol. 1989 Apr;108(4):1431–1444. doi: 10.1083/jcb.108.4.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]

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