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. 1997 Oct;179(20):6325–6334. doi: 10.1128/jb.179.20.6325-6334.1997

Rapamycin specifically interferes with the developmental response of fission yeast to starvation.

R Weisman 1, M Choder 1, Y Koltin 1
PMCID: PMC179546  PMID: 9335279

Abstract

Rapamycin is a microbial macrolide which belongs to a family of immunosuppressive drugs that suppress the immune system by blocking stages of signal transduction in T lymphocytes. In Saccharomyces cerevisiae cells, as in T lymphocytes, rapamycin inhibits growth and cells become arrested at the G1 stage of the cell cycle. Rapamycin is also an effective antifungal agent, affecting the growth of yeast and filamentous fungi. Unexpectedly, we observed that rapamycin has no apparent effect on the vegetative growth of Schizosaccharomyces pombe. Instead, the drug becomes effective only when cells experience starvation. Under such conditions, homothallic wild-type cells will normally mate and undergo sporulation. In the presence of rapamycin, this sexual development process is strongly inhibited and cells adopt an alternative physiological option and enter stationary phase. Rapamycin strongly inhibits sexual development of haploid cells prior to the stage of sexual conjugation. In contrast, the drug has only a slight inhibitory effect on the sporulation of diploid cells. A genetic approach was applied to identify the signal transduction pathway that is inhibited by rapamycin. The results indicate that either rapamycin did not suppress the derepression of sexual development of strains in which adenylate cyclase was deleted or the cyclic AMP-dependent protein kinase encoded by pka1 was mutated. Nor did rapamycin inhibit the unscheduled meiosis observed in pat1-114 mutants. Overexpression of ras1+, an essential gene for sexual development, did not rescue the sterility of rapamycin-treated cells. However, expression of the activated allele, ras1Val17, antagonized the effect of rapamycin and restored the ability of the cells to respond to mating signals in the presence of the drug. We discuss possible mechanisms for the inhibitory effect of rapamycin on sexual development in S. pombe.

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Selected References

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  1. Abraham R. T., Wiederrecht G. J. Immunopharmacology of rapamycin. Annu Rev Immunol. 1996;14:483–510. doi: 10.1146/annurev.immunol.14.1.483. [DOI] [PubMed] [Google Scholar]
  2. Albers M. W., Williams R. T., Brown E. J., Tanaka A., Hall F. L., Schreiber S. L. FKBP-rapamycin inhibits a cyclin-dependent kinase activity and a cyclin D1-Cdk association in early G1 of an osteosarcoma cell line. J Biol Chem. 1993 Oct 25;268(30):22825–22829. [PubMed] [Google Scholar]
  3. Barbet N. C., Schneider U., Helliwell S. B., Stansfield I., Tuite M. F., Hall M. N. TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell. 1996 Jan;7(1):25–42. doi: 10.1091/mbc.7.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beretta L., Gingras A. C., Svitkin Y. V., Hall M. N., Sonenberg N. Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J. 1996 Feb 1;15(3):658–664. [PMC free article] [PubMed] [Google Scholar]
  5. Bierer B. E., Mattila P. S., Standaert R. F., Herzenberg L. A., Burakoff S. J., Crabtree G., Schreiber S. L. Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9231–9235. doi: 10.1073/pnas.87.23.9231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brazelton T. R., Morris R. E. Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol. 1996 Oct;8(5):710–720. doi: 10.1016/s0952-7915(96)80090-2. [DOI] [PubMed] [Google Scholar]
  7. Brown E. J., Albers M. W., Shin T. B., Ichikawa K., Keith C. T., Lane W. S., Schreiber S. L. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature. 1994 Jun 30;369(6483):756–758. doi: 10.1038/369756a0. [DOI] [PubMed] [Google Scholar]
  8. Brown E. J., Beal P. A., Keith C. T., Chen J., Shin T. B., Schreiber S. L. Control of p70 s6 kinase by kinase activity of FRAP in vivo. Nature. 1995 Oct 5;377(6548):441–446. doi: 10.1038/377441a0. [DOI] [PubMed] [Google Scholar]
  9. Brunn G. J., Williams J., Sabers C., Wiederrecht G., Lawrence J. C., Jr, Abraham R. T. Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. EMBO J. 1996 Oct 1;15(19):5256–5267. [PMC free article] [PubMed] [Google Scholar]
  10. Cafferkey R., Young P. R., McLaughlin M. M., Bergsma D. J., Koltin Y., Sathe G. M., Faucette L., Eng W. K., Johnson R. K., Livi G. P. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol Cell Biol. 1993 Oct;13(10):6012–6023. doi: 10.1128/mcb.13.10.6012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Calvo V., Crews C. M., Vik T. A., Bierer B. E. Interleukin 2 stimulation of p70 S6 kinase activity is inhibited by the immunosuppressant rapamycin. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7571–7575. doi: 10.1073/pnas.89.16.7571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cardenas M. E., Muir R. S., Breuder T., Heitman J. Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A. EMBO J. 1995 Jun 15;14(12):2772–2783. doi: 10.1002/j.1460-2075.1995.tb07277.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chiu M. I., Katz H., Berlin V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12574–12578. doi: 10.1073/pnas.91.26.12574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chung J., Kuo C. J., Crabtree G. R., Blenis J. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell. 1992 Jun 26;69(7):1227–1236. doi: 10.1016/0092-8674(92)90643-q. [DOI] [PubMed] [Google Scholar]
  15. Clipstone N. A., Crabtree G. R. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature. 1992 Jun 25;357(6380):695–697. doi: 10.1038/357695a0. [DOI] [PubMed] [Google Scholar]
  16. DeVoti J., Seydoux G., Beach D., McLeod M. Interaction between ran1+ protein kinase and cAMP dependent protein kinase as negative regulators of fission yeast meiosis. EMBO J. 1991 Dec;10(12):3759–3768. doi: 10.1002/j.1460-2075.1991.tb04945.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Di Como C. J., Arndt K. T. Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases. Genes Dev. 1996 Aug 1;10(15):1904–1916. doi: 10.1101/gad.10.15.1904. [DOI] [PubMed] [Google Scholar]
  18. Downward J. Signal transduction. Regulating S6 kinase. Nature. 1994 Sep 29;371(6496):378–379. doi: 10.1038/371378a0. [DOI] [PubMed] [Google Scholar]
  19. Dumont F. J., Staruch M. J., Koprak S. L., Melino M. R., Sigal N. H. Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. J Immunol. 1990 Jan 1;144(1):251–258. [PubMed] [Google Scholar]
  20. Ferrari S., Pearson R. B., Siegmann M., Kozma S. C., Thomas G. The immunosuppressant rapamycin induces inactivation of p70s6k through dephosphorylation of a novel set of sites. J Biol Chem. 1993 Aug 5;268(22):16091–16094. [PubMed] [Google Scholar]
  21. Feuerstein N., Huang D., Prystowsky M. B. Rapamycin selectively blocks interleukin-2-induced proliferating cell nuclear antigen gene expression in T lymphocyte. Evidence for inhibition of CREB/ATF binding activities. J Biol Chem. 1995 Apr 21;270(16):9454–9458. doi: 10.1074/jbc.270.16.9454. [DOI] [PubMed] [Google Scholar]
  22. Foor F., Parent S. A., Morin N., Dahl A. M., Ramadan N., Chrebet G., Bostian K. A., Nielsen J. B. Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from alpha-factor arrest in yeast. Nature. 1992 Dec 17;360(6405):682–684. doi: 10.1038/360682a0. [DOI] [PubMed] [Google Scholar]
  23. Fukui Y., Kaziro Y., Yamamoto M. Mating pheromone-like diffusible factor released by Schizosaccharomyces pombe. EMBO J. 1986 Aug;5(8):1991–1993. doi: 10.1002/j.1460-2075.1986.tb04454.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Fukui Y., Kozasa T., Kaziro Y., Takeda T., Yamamoto M. Role of a ras homolog in the life cycle of Schizosaccharomyces pombe. Cell. 1986 Jan 31;44(2):329–336. doi: 10.1016/0092-8674(86)90767-1. [DOI] [PubMed] [Google Scholar]
  25. Galat A. Peptidylproline cis-trans-isomerases: immunophilins. Eur J Biochem. 1993 Sep 15;216(3):689–707. doi: 10.1111/j.1432-1033.1993.tb18189.x. [DOI] [PubMed] [Google Scholar]
  26. Gotoh Y., Nishida E., Shimanuki M., Toda T., Imai Y., Yamamoto M. Schizosaccharomyces pombe Spk1 is a tyrosine-phosphorylated protein functionally related to Xenopus mitogen-activated protein kinase. Mol Cell Biol. 1993 Oct;13(10):6427–6434. doi: 10.1128/mcb.13.10.6427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Heitman J., Movva N. R., Hall M. N. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science. 1991 Aug 23;253(5022):905–909. doi: 10.1126/science.1715094. [DOI] [PubMed] [Google Scholar]
  28. Helliwell S. B., Wagner P., Kunz J., Deuter-Reinhard M., Henriquez R., Hall M. N. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol Biol Cell. 1994 Jan;5(1):105–118. doi: 10.1091/mbc.5.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hughes D. A., Fukui Y., Yamamoto M. Homologous activators of ras in fission and budding yeast. Nature. 1990 Mar 22;344(6264):355–357. doi: 10.1038/344355a0. [DOI] [PubMed] [Google Scholar]
  30. Iino Y., Yamamoto M. Negative control for the initiation of meiosis in Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2447–2451. doi: 10.1073/pnas.82.8.2447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Jefferies H. B., Reinhard C., Kozma S. C., Thomas G. Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4441–4445. doi: 10.1073/pnas.91.10.4441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kohli J., Hottinger H., Munz P., Strauss A., Thuriaux P. Genetic Mapping in SCHIZOSACCHAROMYCES POMBE by Mitotic and Meiotic Analysis and Induced Haploidization. Genetics. 1977 Nov;87(3):471–489. doi: 10.1093/genetics/87.3.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Koltin Y., Faucette L., Bergsma D. J., Levy M. A., Cafferkey R., Koser P. L., Johnson R. K., Livi G. P. Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein. Mol Cell Biol. 1991 Mar;11(3):1718–1723. doi: 10.1128/mcb.11.3.1718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Koser P. L., Bergsma D. J., Cafferkey R., Eng W. K., McLaughlin M. M., Ferrara A., Silverman C., Kasyan K., Bossard M. J., Johnson R. K. The CYP2 gene of Saccharomyces cerevisiae encodes a cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase with an N-terminal signal sequence. Gene. 1991 Dec 1;108(1):73–80. doi: 10.1016/0378-1119(91)90489-x. [DOI] [PubMed] [Google Scholar]
  35. Kunz J., Hall M. N. Cyclosporin A, FK506 and rapamycin: more than just immunosuppression. Trends Biochem Sci. 1993 Sep;18(9):334–338. doi: 10.1016/0968-0004(93)90069-y. [DOI] [PubMed] [Google Scholar]
  36. Kunz J., Henriquez R., Schneider U., Deuter-Reinhard M., Movva N. R., Hall M. N. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell. 1993 May 7;73(3):585–596. doi: 10.1016/0092-8674(93)90144-f. [DOI] [PubMed] [Google Scholar]
  37. Kuo C. J., Chung J., Fiorentino D. F., Flanagan W. M., Blenis J., Crabtree G. R. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature. 1992 Jul 2;358(6381):70–73. doi: 10.1038/358070a0. [DOI] [PubMed] [Google Scholar]
  38. LEUPOLD U. Methodisches zur Genetik von Schizosaccharomyces pombe. Schweiz Z Pathol Bakteriol. 1955;18(5):1141–1146. [PubMed] [Google Scholar]
  39. Leupold U., Sipiczki M., Egel R. Pheromone production and response in sterile mutants of fission yeast. Curr Genet. 1991 Jul;20(1-2):79–85. doi: 10.1007/BF00312769. [DOI] [PubMed] [Google Scholar]
  40. Lin T. A., Kong X., Saltiel A. R., Blackshear P. J., Lawrence J. C., Jr Control of PHAS-I by insulin in 3T3-L1 adipocytes. Synthesis, degradation, and phosphorylation by a rapamycin-sensitive and mitogen-activated protein kinase-independent pathway. J Biol Chem. 1995 Aug 4;270(31):18531–18538. doi: 10.1074/jbc.270.31.18531. [DOI] [PubMed] [Google Scholar]
  41. MacNeill S. A., Warbrick E., Fantes P. A. Controlling cell cycle progress in the fission yeast Schizosaccharomyces pombe. Curr Opin Genet Dev. 1991 Oct;1(3):307–312. doi: 10.1016/s0959-437x(05)80292-8. [DOI] [PubMed] [Google Scholar]
  42. Maeda T., Watanabe Y., Kunitomo H., Yamamoto M. Cloning of the pka1 gene encoding the catalytic subunit of the cAMP-dependent protein kinase in Schizosaccharomyces pombe. J Biol Chem. 1994 Apr 1;269(13):9632–9637. [PubMed] [Google Scholar]
  43. Martin-Castellanos C., Labib K., Moreno S. B-type cyclins regulate G1 progression in fission yeast in opposition to the p25rum1 cdk inhibitor. EMBO J. 1996 Feb 15;15(4):839–849. [PMC free article] [PubMed] [Google Scholar]
  44. McCaffrey P. G., Perrino B. A., Soderling T. R., Rao A. NF-ATp, a T lymphocyte DNA-binding protein that is a target for calcineurin and immunosuppressive drugs. J Biol Chem. 1993 Feb 15;268(5):3747–3752. [PubMed] [Google Scholar]
  45. McLeod M., Beach D. A specific inhibitor of the ran1+ protein kinase regulates entry into meiosis in Schizosaccharomyces pombe. Nature. 1988 Apr 7;332(6164):509–514. doi: 10.1038/332509a0. [DOI] [PubMed] [Google Scholar]
  46. Ming X. F., Burgering B. M., Wennström S., Claesson-Welsh L., Heldin C. H., Bos J. L., Kozma S. C., Thomas G. Activation of p70/p85 S6 kinase by a pathway independent of p21ras. Nature. 1994 Sep 29;371(6496):426–429. doi: 10.1038/371426a0. [DOI] [PubMed] [Google Scholar]
  47. Molnar M., Sipiczki M. Two novel genes involved in the sexual development of Schizosaccharomyces pombe. Curr Genet. 1995 Oct;28(5):447–453. doi: 10.1007/BF00310814. [DOI] [PubMed] [Google Scholar]
  48. Moreno S., Klar A., Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l. [DOI] [PubMed] [Google Scholar]
  49. Morice W. G., Wiederrecht G., Brunn G. J., Siekierka J. J., Abraham R. T. Rapamycin inhibition of interleukin-2-dependent p33cdk2 and p34cdc2 kinase activation in T lymphocytes. J Biol Chem. 1993 Oct 25;268(30):22737–22745. [PubMed] [Google Scholar]
  50. Nadin-Davis S. A., Nasim A., Beach D. Involvement of ras in sexual differentiation but not in growth control in fission yeast. EMBO J. 1986 Nov;5(11):2963–2971. doi: 10.1002/j.1460-2075.1986.tb04593.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Nadin-Davis S. A., Nasim A. Schizosaccharomyces pombe ras1 and byr1 are functionally related genes of the ste family that affect starvation-induced transcription of mating-type genes. Mol Cell Biol. 1990 Feb;10(2):549–560. doi: 10.1128/mcb.10.2.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Nielsen O., Davey J., Egel R. The ras1 function of Schizosaccharomyces pombe mediates pheromone-induced transcription. EMBO J. 1992 Apr;11(4):1391–1395. doi: 10.1002/j.1460-2075.1992.tb05184.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Nourse J., Firpo E., Flanagan W. M., Coats S., Polyak K., Lee M. H., Massague J., Crabtree G. R., Roberts J. M. Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature. 1994 Dec 8;372(6506):570–573. doi: 10.1038/372570a0. [DOI] [PubMed] [Google Scholar]
  54. Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. doi: 10.1038/344503a0. [DOI] [PubMed] [Google Scholar]
  55. Prentice H. L. High efficiency transformation of Schizosaccharomyces pombe by electroporation. Nucleic Acids Res. 1992 Feb 11;20(3):621–621. doi: 10.1093/nar/20.3.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Price D. J., Grove J. R., Calvo V., Avruch J., Bierer B. E. Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase. Science. 1992 Aug 14;257(5072):973–977. doi: 10.1126/science.1380182. [DOI] [PubMed] [Google Scholar]
  57. Russell P., Nurse P. Schizosaccharomyces pombe and Saccharomyces cerevisiae: a look at yeasts divided. Cell. 1986 Jun 20;45(6):781–782. doi: 10.1016/0092-8674(86)90550-7. [DOI] [PubMed] [Google Scholar]
  58. Sabatini D. M., Erdjument-Bromage H., Lui M., Tempst P., Snyder S. H. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell. 1994 Jul 15;78(1):35–43. doi: 10.1016/0092-8674(94)90570-3. [DOI] [PubMed] [Google Scholar]
  59. Sabers C. J., Martin M. M., Brunn G. J., Williams J. M., Dumont F. J., Wiederrecht G., Abraham R. T. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem. 1995 Jan 13;270(2):815–822. doi: 10.1074/jbc.270.2.815. [DOI] [PubMed] [Google Scholar]
  60. Schreiber S. L., Crabtree G. R. The mechanism of action of cyclosporin A and FK506. Immunol Today. 1992 Apr;13(4):136–142. doi: 10.1016/0167-5699(92)90111-J. [DOI] [PubMed] [Google Scholar]
  61. Sigal N. H., Dumont F. J. Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction. Annu Rev Immunol. 1992;10:519–560. doi: 10.1146/annurev.iy.10.040192.002511. [DOI] [PubMed] [Google Scholar]
  62. Stettler S., Warbrick E., Prochnik S., Mackie S., Fantes P. The wis1 signal transduction pathway is required for expression of cAMP-repressed genes in fission yeast. J Cell Sci. 1996 Jul;109(Pt 7):1927–1935. doi: 10.1242/jcs.109.7.1927. [DOI] [PubMed] [Google Scholar]
  63. Terada N., Patel H. R., Takase K., Kohno K., Nairn A. C., Gelfand E. W. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11477–11481. doi: 10.1073/pnas.91.24.11477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Tropschug M., Barthelmess I. B., Neupert W. Sensitivity to cyclosporin A is mediated by cyclophilin in Neurospora crassa and Saccharomyces cerevisiae. Nature. 1989 Dec 21;342(6252):953–955. doi: 10.1038/342953a0. [DOI] [PubMed] [Google Scholar]
  65. Wang Y., Xu H. P., Riggs M., Rodgers L., Wigler M. byr2, a Schizosaccharomyces pombe gene encoding a protein kinase capable of partial suppression of the ras1 mutant phenotype. Mol Cell Biol. 1991 Jul;11(7):3554–3563. doi: 10.1128/mcb.11.7.3554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Weisman R., Creanor J., Fantes P. A multicopy suppressor of a cell cycle defect in S. pombe encodes a heat shock-inducible 40 kDa cyclophilin-like protein. EMBO J. 1996 Feb 1;15(3):447–456. [PMC free article] [PubMed] [Google Scholar]
  67. Wu L., Russell P. Roles of Wee1 and Nim1 protein kinases in regulating the switch from mitotic division to sexual development in Schizosaccharomyces pombe. Mol Cell Biol. 1997 Jan;17(1):10–17. doi: 10.1128/mcb.17.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Xu H. P., White M., Marcus S., Wigler M. Concerted action of RAS and G proteins in the sexual response pathways of Schizosaccharomyces pombe. Mol Cell Biol. 1994 Jan;14(1):50–58. doi: 10.1128/mcb.14.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Yamamoto M. The molecular control mechanisms of meiosis in fission yeast. Trends Biochem Sci. 1996 Jan;21(1):18–22. [PubMed] [Google Scholar]
  70. Yoshida T., Toda T., Yanagida M. A calcineurin-like gene ppb1+ in fission yeast: mutant defects in cytokinesis, cell polarity, mating and spindle pole body positioning. J Cell Sci. 1994 Jul;107(Pt 7):1725–1735. doi: 10.1242/jcs.107.7.1725. [DOI] [PubMed] [Google Scholar]
  71. de Groot R. P., Ballou L. M., Sassone-Corsi P. Positive regulation of the cAMP-responsive activator CREM by the p70 S6 kinase: an alternative route to mitogen-induced gene expression. Cell. 1994 Oct 7;79(1):81–91. doi: 10.1016/0092-8674(94)90402-2. [DOI] [PubMed] [Google Scholar]

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