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. 1990 Oct;9(10):3233–3240. doi: 10.1002/j.1460-2075.1990.tb07522.x

p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes.

J Shuttleworth 1, R Godfrey 1, A Colman 1
PMCID: PMC552054  PMID: 2209545

Abstract

The clone MO15 which codes for a 40 kd protein (p40MO15) with 40% amino acid identity to the human cdc2 protein kinase has been isolated from a Xenopus cDNA library using a synthetic oligonucleotide probe. MO15 mRNA is accumulated during oogenesis, becomes de-adenylated during meiotic maturation, and is degraded after the mid-blastula-transition stage of embryogenesis. Translation of p40MO15 is restricted to non-mature oocytes. Specific inhibition of p40MO15 synthesis in stage VI oocytes by antisense oligonucleotide depletion of MO15 mRNA increases the rate of progesterone induced H1 kinase activation and oocyte maturation. This effect can be reversed by subsequent injection of synthetic MO15 mRNA. These results suggest that p40MO15 is involved in negatively regulating meiosis.

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Selected References

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

  1. Bailly E., Dorée M., Nurse P., Bornens M. p34cdc2 is located in both nucleus and cytoplasm; part is centrosomally associated at G2/M and enters vesicles at anaphase. EMBO J. 1989 Dec 20;8(13):3985–3995. doi: 10.1002/j.1460-2075.1989.tb08581.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Boyer J., Asselin J., Bellé R., Ozon R. Progesterone and cAMP-dependent protein kinase regulate in vivo the level of phosphorylation of two proteins (Mr 20,000 and Mr 32,000) in Xenopus oocytes. Dev Biol. 1986 Feb;113(2):420–428. doi: 10.1016/0012-1606(86)90176-4. [DOI] [PubMed] [Google Scholar]
  4. Courchesne W. E., Kunisawa R., Thorner J. A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae. Cell. 1989 Sep 22;58(6):1107–1119. doi: 10.1016/0092-8674(89)90509-6. [DOI] [PubMed] [Google Scholar]
  5. Cyert M. S., Kirschner M. W. Regulation of MPF activity in vitro. Cell. 1988 Apr 22;53(2):185–195. doi: 10.1016/0092-8674(88)90380-7. [DOI] [PubMed] [Google Scholar]
  6. Dale L., Matthews G., Tabe L., Colman A. Developmental expression of the protein product of Vg1, a localized maternal mRNA in the frog Xenopus laevis. EMBO J. 1989 Apr;8(4):1057–1065. doi: 10.1002/j.1460-2075.1989.tb03473.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dash P., Lotan I., Knapp M., Kandel E. R., Goelet P. Selective elimination of mRNAs in vivo: complementary oligodeoxynucleotides promote RNA degradation by an RNase H-like activity. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7896–7900. doi: 10.1073/pnas.84.22.7896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis F. M., Tsao T. Y., Fowler S. K., Rao P. N. Monoclonal antibodies to mitotic cells. Proc Natl Acad Sci U S A. 1983 May;80(10):2926–2930. doi: 10.1073/pnas.80.10.2926. [DOI] [PMC free article] [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. Dunphy W. G., Brizuela L., Beach D., Newport J. The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis. Cell. 1988 Jul 29;54(3):423–431. doi: 10.1016/0092-8674(88)90205-x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Dworkin M. B., Dworkin-Rastl E. Changes in RNA titers and polyadenylation during oogenesis and oocyte maturation in Xenopus laevis. Dev Biol. 1985 Dec;112(2):451–457. doi: 10.1016/0012-1606(85)90417-8. [DOI] [PubMed] [Google Scholar]
  13. Elion E. A., Grisafi P. L., Fink G. R. FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation. Cell. 1990 Feb 23;60(4):649–664. doi: 10.1016/0092-8674(90)90668-5. [DOI] [PubMed] [Google Scholar]
  14. Félix M. A., Cohen P., Karsenti E. Cdc2 H1 kinase is negatively regulated by a type 2A phosphatase in the Xenopus early embryonic cell cycle: evidence from the effects of okadaic acid. EMBO J. 1990 Mar;9(3):675–683. doi: 10.1002/j.1460-2075.1990.tb08159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gautier J., Matsukawa T., Nurse P., Maller J. Dephosphorylation and activation of Xenopus p34cdc2 protein kinase during the cell cycle. Nature. 1989 Jun 22;339(6226):626–629. doi: 10.1038/339626a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Gautier J., Norbury C., Lohka M., Nurse P., Maller J. Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+. Cell. 1988 Jul 29;54(3):433–439. doi: 10.1016/0092-8674(88)90206-1. [DOI] [PubMed] [Google Scholar]
  18. Goris J., Hermann J., Hendrix P., Ozon R., Merlevede W. Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes. FEBS Lett. 1989 Mar 13;245(1-2):91–94. doi: 10.1016/0014-5793(89)80198-x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Gurdon J. B. The croonian lecture, 1976. Egg cytoplasm and gene control in development. Proc R Soc Lond B Biol Sci. 1977 Sep 5;198(1132):211–247. doi: 10.1098/rspb.1977.0095. [DOI] [PubMed] [Google Scholar]
  21. Hanks S. K. Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family. Proc Natl Acad Sci U S A. 1987 Jan;84(2):388–392. doi: 10.1073/pnas.84.2.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  23. Hindley J., Phear G. A. Sequence of the cell division gene CDC2 from Schizosaccharomyces pombe; patterns of splicing and homology to protein kinases. Gene. 1984 Nov;31(1-3):129–134. doi: 10.1016/0378-1119(84)90203-8. [DOI] [PubMed] [Google Scholar]
  24. Horrell A., Shuttleworth J., Colman A. Transcript levels and translational control of hsp70 synthesis in Xenopus oocytes. Genes Dev. 1987 Jul;1(5):433–444. doi: 10.1101/gad.1.5.433. [DOI] [PubMed] [Google Scholar]
  25. Hunt T. Maturation promoting factor, cyclin and the control of M-phase. Curr Opin Cell Biol. 1989 Apr;1(2):268–274. doi: 10.1016/0955-0674(89)90099-9. [DOI] [PubMed] [Google Scholar]
  26. Hyman L. E., Wormington W. M. Translational inactivation of ribosomal protein mRNAs during Xenopus oocyte maturation. Genes Dev. 1988 May;2(5):598–605. doi: 10.1101/gad.2.5.598. [DOI] [PubMed] [Google Scholar]
  27. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kressmann A., Clarkson S. G., Pirrotta V., Birnstiel M. L. Transcription of cloned tRNA gene fragments and subfragments injected into the oocyte nucleus of Xenopus laevis. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1176–1180. doi: 10.1073/pnas.75.3.1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Krieg P. A., Melton D. A. Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. Nucleic Acids Res. 1984 Sep 25;12(18):7057–7070. doi: 10.1093/nar/12.18.7057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  31. LaMarca M. J., Westphal L. M., Rein D. A. Gonadotropins and the timing of progesterone-induced meiotic maturation of Xenopus laevis oocytes. Dev Biol. 1985 May;109(1):32–40. doi: 10.1016/0012-1606(85)90343-4. [DOI] [PubMed] [Google Scholar]
  32. Lee M. G., Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987 May 7;327(6117):31–35. doi: 10.1038/327031a0. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Maller J. L., Krebs E. G. Progesterone-stimulated meiotic cell division in Xenopus oocytes. Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase. J Biol Chem. 1977 Mar 10;252(5):1712–1718. [PubMed] [Google Scholar]
  35. Maller J. L., Smith D. S. Two-dimensional polyacrylamide gel analysis of changes in protein phosphorylation during maturation of Xenopus oocytes. Dev Biol. 1985 May;109(1):150–156. doi: 10.1016/0012-1606(85)90355-0. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Minshull J., Blow J. J., Hunt T. Translation of cyclin mRNA is necessary for extracts of activated xenopus eggs to enter mitosis. Cell. 1989 Mar 24;56(6):947–956. doi: 10.1016/0092-8674(89)90628-4. [DOI] [PubMed] [Google Scholar]
  38. Moreno S., Hayles J., Nurse P. Regulation of p34cdc2 protein kinase during mitosis. Cell. 1989 Jul 28;58(2):361–372. doi: 10.1016/0092-8674(89)90850-7. [DOI] [PubMed] [Google Scholar]
  39. Moreno S., Nurse P. Substrates for p34cdc2: in vivo veritas? Cell. 1990 May 18;61(4):549–551. doi: 10.1016/0092-8674(90)90463-o. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Murray A. W. Cell biology: the cell cycle as a cdc2 cycle. Nature. 1989 Nov 2;342(6245):14–15. doi: 10.1038/342014a0. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Nurse P., Bissett Y. Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast. Nature. 1981 Aug 6;292(5823):558–560. doi: 10.1038/292558a0. [DOI] [PubMed] [Google Scholar]
  44. Peter M., Nakagawa J., Dorée M., Labbé J. C., Nigg E. A. In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. Cell. 1990 May 18;61(4):591–602. doi: 10.1016/0092-8674(90)90471-p. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Reynhout J. K., Taddei C., Smith L. D., LaMarca M. J. Response of large oocytes of Xenopus laevis to progesterone in vitro in relation to oocyte size and time after previous HCG-induced ovulation. Dev Biol. 1975 Jun;44(2):375–379. doi: 10.1016/0012-1606(75)90408-x. [DOI] [PubMed] [Google Scholar]
  47. Rosenberg A. H., Lade B. N., Chui D. S., Lin S. W., Dunn J. J., Studier F. W. Vectors for selective expression of cloned DNAs by T7 RNA polymerase. Gene. 1987;56(1):125–135. doi: 10.1016/0378-1119(87)90165-x. [DOI] [PubMed] [Google Scholar]
  48. Sagata N., Daar I., Oskarsson M., Showalter S. D., Vande Woude G. F. The product of the mos proto-oncogene as a candidate "initiator" for oocyte maturation. Science. 1989 Aug 11;245(4918):643–646. doi: 10.1126/science.2474853. [DOI] [PubMed] [Google Scholar]
  49. Shuttleworth J., Colman A. Antisense oligonucleotide-directed cleavage of mRNA in Xenopus oocytes and eggs. EMBO J. 1988 Feb;7(2):427–434. doi: 10.1002/j.1460-2075.1988.tb02830.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Simon M., Seraphin B., Faye G. KIN28, a yeast split gene coding for a putative protein kinase homologous to CDC28. EMBO J. 1986 Oct;5(10):2697–2701. doi: 10.1002/j.1460-2075.1986.tb04553.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Smith L. D. The induction of oocyte maturation: transmembrane signaling events and regulation of the cell cycle. Development. 1989 Dec;107(4):685–699. doi: 10.1242/dev.107.4.685. [DOI] [PubMed] [Google Scholar]
  52. Spivack J. G., Erikson R. L., Maller J. L. Microinjection of pp60v-src into Xenopus oocytes increases phosphorylation of ribosomal protein S6 and accelerates the rate of progesterone-induced meiotic maturation. Mol Cell Biol. 1984 Aug;4(8):1631–1634. doi: 10.1128/mcb.4.8.1631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Studier F. W., Moffatt B. A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. doi: 10.1016/0022-2836(86)90385-2. [DOI] [PubMed] [Google Scholar]
  54. Toh-e A., Tanaka K., Uesono Y., Wickner R. B. PHO85, a negative regulator of the PHO system, is a homolog of the protein kinase gene, CDC28, of Saccharomyces cerevisiae. Mol Gen Genet. 1988 Sep;214(1):162–164. doi: 10.1007/BF00340196. [DOI] [PubMed] [Google Scholar]
  55. Wasserman W. J., Masui Y. Effects of cyclohexamide on a cytoplasmic factor initiating meiotic naturation in Xenopus oocytes. Exp Cell Res. 1975 Mar 15;91(2):381–388. doi: 10.1016/0014-4827(75)90118-4. [DOI] [PubMed] [Google Scholar]
  56. Watanabe N., Vande Woude G. F., Ikawa Y., Sagata N. Specific proteolysis of the c-mos proto-oncogene product by calpain on fertilization of Xenopus eggs. Nature. 1989 Nov 30;342(6249):505–511. doi: 10.1038/342505a0. [DOI] [PubMed] [Google Scholar]
  57. Woolf T. M., Jennings C. G., Rebagliati M., Melton D. A. The stability, toxicity and effectiveness of unmodified and phosphorothioate antisense oligodeoxynucleotides in Xenopus oocytes and embryos. Nucleic Acids Res. 1990 Apr 11;18(7):1763–1769. doi: 10.1093/nar/18.7.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]

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