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. 1992 Mar;3(3):263–273. doi: 10.1091/mbc.3.3.263

Fission yeast sts1+ gene encodes a protein similar to the chicken lamin B receptor and is implicated in pleiotropic drug-sensitivity, divalent cation-sensitivity, and osmoregulation.

M Shimanuki 1, M Goebl 1, M Yanagida 1, T Toda 1
PMCID: PMC275528  PMID: 1320960

Abstract

The Schizosaccharomyces pombe sts1+ gene, identified by supersensitive mutations to a protein kinase inhibitor, staurosporine, was isolated by complementation by the use of a fission yeast genomic library. Nucleotide sequencing shows that the sts1+ gene encodes a 453 amino acid putative membrane-associated protein that is significantly similar (26% identity) to the chicken lamin B receptor. It is also highly related (53% identity) to a budding yeast ORF, YGL022. These three proteins contain a similar hydrophobicity pattern consisting of eight or nine putative transmembrane domains. By gene disruption we demonstrate that the sts1+ gene is not essential for viability. These disruptants exhibit pleiotropic defects, such as cold-sensitivity for growth and at the permissive temperature, a supersensitivity to divalent cations and several unrelated drugs including staurosporine, caffeine, chloramphenicol, sorbitol, and SDS. Disruption of the sts1+ gene does not lead to a sensitivity to thiabendazole or hydroxyurea.

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Selected References

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  1. Balzi E., Chen W., Ulaszewski S., Capieaux E., Goffeau A. The multidrug resistance gene PDR1 from Saccharomyces cerevisiae. J Biol Chem. 1987 Dec 15;262(35):16871–16879. [PubMed] [Google Scholar]
  2. Banta L. M., Vida T. A., Herman P. K., Emr S. D. Characterization of yeast Vps33p, a protein required for vacuolar protein sorting and vacuole biogenesis. Mol Cell Biol. 1990 Sep;10(9):4638–4649. doi: 10.1128/mcb.10.9.4638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beach D., Piper M., Nurse P. Construction of a Schizosaccharomyces pombe gene bank in a yeast bacterial shuttle vector and its use to isolate genes by complementation. Mol Gen Genet. 1982;187(2):326–329. doi: 10.1007/BF00331138. [DOI] [PubMed] [Google Scholar]
  4. Boulton T. G., Nye S. H., Robbins D. J., Ip N. Y., Radziejewska E., Morgenbesser S. D., DePinho R. A., Panayotatos N., Cobb M. H., Yancopoulos G. D. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell. 1991 May 17;65(4):663–675. doi: 10.1016/0092-8674(91)90098-j. [DOI] [PubMed] [Google Scholar]
  5. Boulton T. G., Yancopoulos G. D., Gregory J. S., Slaughter C., Moomaw C., Hsu J., Cobb M. H. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science. 1990 Jul 6;249(4964):64–67. doi: 10.1126/science.2164259. [DOI] [PubMed] [Google Scholar]
  6. Chen W. N., Balzi E., Capieaux E., Choder M., Goffeau A. The DNA sequencing of the 17 kb HindIII fragment spanning the LEU1 and ATE1 loci on chromosome VII from Saccharomyces cerevisiae reveals the PDR6 gene, a new member of the genetic network controlling pleiotropic drug resistance. Yeast. 1991 Apr;7(3):287–299. doi: 10.1002/yea.320070311. [DOI] [PubMed] [Google Scholar]
  7. Chen W. N., Capieaux E., Balzi E., Goffeau A. The YGL022 gene encodes a putative transport protein. Yeast. 1991 Apr;7(3):305–308. doi: 10.1002/yea.320070313. [DOI] [PubMed] [Google Scholar]
  8. Chikashige Y., Kinoshita N., Nakaseko Y., Matsumoto T., Murakami S., Niwa O., Yanagida M. Composite motifs and repeat symmetry in S. pombe centromeres: direct analysis by integration of NotI restriction sites. Cell. 1989 Jun 2;57(5):739–751. doi: 10.1016/0092-8674(89)90789-7. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Diffley J. F., Stillman B. Transcriptional silencing and lamins. Nature. 1989 Nov 2;342(6245):24–24. doi: 10.1038/342024a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Endicott J. A., Ling V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem. 1989;58:137–171. doi: 10.1146/annurev.bi.58.070189.001033. [DOI] [PubMed] [Google Scholar]
  13. Enoch T., Peter M., Nurse P., Nigg E. A. p34cdc2 acts as a lamin kinase in fission yeast. J Cell Biol. 1991 Mar;112(5):797–807. doi: 10.1083/jcb.112.5.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Georgatos S. D., Maroulakou I., Blobel G. Lamin A, lamin B, and lamin B receptor analogues in yeast. J Cell Biol. 1989 Jun;108(6):2069–2082. doi: 10.1083/jcb.108.6.2069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gerace L., Burke B. Functional organization of the nuclear envelope. Annu Rev Cell Biol. 1988;4:335–374. doi: 10.1146/annurev.cb.04.110188.002003. [DOI] [PubMed] [Google Scholar]
  16. Ghislain M., Schlesser A., Goffeau A. Mutation of a conserved glycine residue modifies the vanadate sensitivity of the plasma membrane H+-ATPase from Schizosaccharomyces pombe. J Biol Chem. 1987 Dec 25;262(36):17549–17555. [PubMed] [Google Scholar]
  17. Grimm C., Kohli J., Murray J., Maundrell K. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker. Mol Gen Genet. 1988 Dec;215(1):81–86. doi: 10.1007/BF00331307. [DOI] [PubMed] [Google Scholar]
  18. Gros P., Ben Neriah Y. B., Croop J. M., Housman D. E. Isolation and expression of a complementary DNA that confers multidrug resistance. Nature. 1986 Oct 23;323(6090):728–731. doi: 10.1038/323728a0. [DOI] [PubMed] [Google Scholar]
  19. Haarer B. K., Pringle J. R. Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10-nm filaments in the mother-bud neck. Mol Cell Biol. 1987 Oct;7(10):3678–3687. doi: 10.1128/mcb.7.10.3678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  21. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  22. Hirano T., Hiraoka Y., Yanagida M. A temperature-sensitive mutation of the Schizosaccharomyces pombe gene nuc2+ that encodes a nuclear scaffold-like protein blocks spindle elongation in mitotic anaphase. J Cell Biol. 1988 Apr;106(4):1171–1183. doi: 10.1083/jcb.106.4.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hiraoka Y., Toda T., Yanagida M. The NDA3 gene of fission yeast encodes beta-tubulin: a cold-sensitive nda3 mutation reversibly blocks spindle formation and chromosome movement in mitosis. Cell. 1984 Dec;39(2 Pt 1):349–358. doi: 10.1016/0092-8674(84)90013-8. [DOI] [PubMed] [Google Scholar]
  24. Hottinger H., Stadelmann B., Pearson D., Frendewey D., Kohli J., Söll D. The Schizosaccharomyces pombe sup3-i suppressor recognizes ochre, but not amber codons in vitro and in vivo. EMBO J. 1984 Feb;3(2):423–428. doi: 10.1002/j.1460-2075.1984.tb01823.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kane P. M., Yamashiro C. T., Stevens T. H. Biochemical characterization of the yeast vacuolar H(+)-ATPase. J Biol Chem. 1989 Nov 15;264(32):19236–19244. [PubMed] [Google Scholar]
  27. Kim H. B., Haarer B. K., Pringle J. R. Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization of the CDC3 gene product and the timing of events at the budding site. J Cell Biol. 1991 Feb;112(4):535–544. doi: 10.1083/jcb.112.4.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Klionsky D. J., Herman P. K., Emr S. D. The fungal vacuole: composition, function, and biogenesis. Microbiol Rev. 1990 Sep;54(3):266–292. doi: 10.1128/mr.54.3.266-292.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  30. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  31. McGrath J. P., Varshavsky A. The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein. Nature. 1989 Aug 3;340(6232):400–404. doi: 10.1038/340400a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Morris N. R., Lai M. H., Oakley C. E. Identification of a gene for alpha-tubulin in Aspergillus nidulans. Cell. 1979 Feb;16(2):437–442. doi: 10.1016/0092-8674(79)90019-9. [DOI] [PubMed] [Google Scholar]
  34. Nakano H., Kobayashi E., Takahashi I., Tamaoki T., Kuzuu Y., Iba H. Staurosporine inhibits tyrosine-specific protein kinase activity of Rous sarcoma virus transforming protein p60. J Antibiot (Tokyo) 1987 May;40(5):706–708. doi: 10.7164/antibiotics.40.706. [DOI] [PubMed] [Google Scholar]
  35. Nasmyth K. A., Reed S. I. Isolation of genes by complementation in yeast: molecular cloning of a cell-cycle gene. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2119–2123. doi: 10.1073/pnas.77.4.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Neff N. F., Thomas J. H., Grisafi P., Botstein D. Isolation of the beta-tubulin gene from yeast and demonstration of its essential function in vivo. Cell. 1983 May;33(1):211–219. doi: 10.1016/0092-8674(83)90350-1. [DOI] [PubMed] [Google Scholar]
  37. Nelson H., Nelson N. Disruption of genes encoding subunits of yeast vacuolar H(+)-ATPase causes conditional lethality. Proc Natl Acad Sci U S A. 1990 May;87(9):3503–3507. doi: 10.1073/pnas.87.9.3503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nelson H., Nelson N. The progenitor of ATP synthases was closely related to the current vacuolar H+-ATPase. FEBS Lett. 1989 Apr 10;247(1):147–153. doi: 10.1016/0014-5793(89)81259-1. [DOI] [PubMed] [Google Scholar]
  39. Nigg E. A. The nuclear envelope. Curr Opin Cell Biol. 1989 Jun;1(3):435–440. doi: 10.1016/0955-0674(89)90002-1. [DOI] [PubMed] [Google Scholar]
  40. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  41. Ohkura H., Kinoshita N., Miyatani S., Toda T., Yanagida M. The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases. Cell. 1989 Jun 16;57(6):997–1007. doi: 10.1016/0092-8674(89)90338-3. [DOI] [PubMed] [Google Scholar]
  42. Ohya Y., Ohsumi Y., Anraku Y. Isolation and characterization of Ca2+-sensitive mutants of Saccharomyces cerevisiae. J Gen Microbiol. 1986 Apr;132(4):979–988. doi: 10.1099/00221287-132-4-979. [DOI] [PubMed] [Google Scholar]
  43. Omura S., Iwai Y., Hirano A., Nakagawa A., Awaya J., Tsuchya H., Takahashi Y., Masuma R. A new alkaloid AM-2282 OF Streptomyces origin. Taxonomy, fermentation, isolation and preliminary characterization. J Antibiot (Tokyo) 1977 Apr;30(4):275–282. doi: 10.7164/antibiotics.30.275. [DOI] [PubMed] [Google Scholar]
  44. Posada J., Sanghera J., Pelech S., Aebersold R., Cooper J. A. Tyrosine phosphorylation and activation of homologous protein kinases during oocyte maturation and mitogenic activation of fibroblasts. Mol Cell Biol. 1991 May;11(5):2517–2528. doi: 10.1128/mcb.11.5.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rothstein R. J. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. doi: 10.1016/0076-6879(83)01015-0. [DOI] [PubMed] [Google Scholar]
  46. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Schatz P. J., Solomon F., Botstein D. Genetically essential and nonessential alpha-tubulin genes specify functionally interchangeable proteins. Mol Cell Biol. 1986 Nov;6(11):3722–3733. doi: 10.1128/mcb.6.11.3722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Serrano R., Kielland-Brandt M. C., Fink G. R. Yeast plasma membrane ATPase is essential for growth and has homology with (Na+ + K+), K+- and Ca2+-ATPases. Nature. 1986 Feb 20;319(6055):689–693. doi: 10.1038/319689a0. [DOI] [PubMed] [Google Scholar]
  49. Sheir-Neiss G., Lai M. H., Morris N. R. Identification of a gene for beta-tubulin in Aspergillus nidulans. Cell. 1978 Oct;15(2):639–647. doi: 10.1016/0092-8674(78)90032-6. [DOI] [PubMed] [Google Scholar]
  50. Tamaoki T., Nomoto H., Takahashi I., Kato Y., Morimoto M., Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):397–402. doi: 10.1016/0006-291x(86)90008-2. [DOI] [PubMed] [Google Scholar]
  51. Thomas J. H., Neff N. F., Botstein D. Isolation and characterization of mutations in the beta-tubulin gene of Saccharomyces cerevisiae. Genetics. 1985 Dec;111(4):715–734. doi: 10.1093/genetics/111.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Toda T., Adachi Y., Hiraoka Y., Yanagida M. Identification of the pleiotropic cell division cycle gene NDA2 as one of two different alpha-tubulin genes in Schizosaccharomyces pombe. Cell. 1984 May;37(1):233–242. doi: 10.1016/0092-8674(84)90319-2. [DOI] [PubMed] [Google Scholar]
  53. Toda T., Shimanuki M., Yanagida M. Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. Genes Dev. 1991 Jan;5(1):60–73. doi: 10.1101/gad.5.1.60. [DOI] [PubMed] [Google Scholar]
  54. Ueda K., Cardarelli C., Gottesman M. M., Pastan I. Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci U S A. 1987 May;84(9):3004–3008. doi: 10.1073/pnas.84.9.3004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Ulaszewski S., Balzi E., Goffeau A. Genetic and molecular mapping of the pma1 mutation conferring vanadate resistance to the plasma membrane ATPase from Saccharomyces cerevisiae. Mol Gen Genet. 1987 Apr;207(1):38–46. doi: 10.1007/BF00331488. [DOI] [PubMed] [Google Scholar]
  56. Umemoto N., Yoshihisa T., Hirata R., Anraku Y. Roles of the VMA3 gene product, subunit c of the vacuolar membrane H(+)-ATPase on vacuolar acidification and protein transport. A study with VMA3-disrupted mutants of Saccharomyces cerevisiae. J Biol Chem. 1990 Oct 25;265(30):18447–18453. [PubMed] [Google Scholar]
  57. Umesono K., Toda T., Hayashi S., Yanagida M. Cell division cycle genes nda2 and nda3 of the fission yeast Schizosaccharomyces pombe control microtubular organization and sensitivity to anti-mitotic benzimidazole compounds. J Mol Biol. 1983 Aug 5;168(2):271–284. doi: 10.1016/s0022-2836(83)80018-7. [DOI] [PubMed] [Google Scholar]
  58. Wada Y., Kitamoto K., Kanbe T., Tanaka K., Anraku Y. The SLP1 gene of Saccharomyces cerevisiae is essential for vacuolar morphogenesis and function. Mol Cell Biol. 1990 May;10(5):2214–2223. doi: 10.1128/mcb.10.5.2214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Worman H. J., Evans C. D., Blobel G. The lamin B receptor of the nuclear envelope inner membrane: a polytopic protein with eight potential transmembrane domains. J Cell Biol. 1990 Oct;111(4):1535–1542. doi: 10.1083/jcb.111.4.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Worman H. J., Yuan J., Blobel G., Georgatos S. D. A lamin B receptor in the nuclear envelope. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8531–8534. doi: 10.1073/pnas.85.22.8531. [DOI] [PMC free article] [PubMed] [Google Scholar]

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