Genetic interactions between Hsp90 and the Cdc2 mitotic machinery in the fission yeast Schizosaccharomyces pombe

被引:45
作者
Muñoz, MJ [1 ]
Jimenez, J [1 ]
机构
[1] Univ Malaga, Fac Ciencias, Unidad Genet, E-29071 Malaga, Spain
来源
MOLECULAR AND GENERAL GENETICS | 1999年 / 261卷 / 02期
关键词
cdc2; swo1; Schizosaccharomyces pombe; Hsp90; mitosis;
D O I
10.1007/s004380050963
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In Schizosaccharomyces ces pombe, wee1 encodes a tyrosine kinase that inhibits entry into mitosis by phophorylating Cdc2, the universal cyclin-dependent kinase (Cdk) that regulates the G2/M transition in all eukaryotic cells. A search for suppressors of the G2 arrest caused by overexpression of wee1 led to the isolation of a new allele of swo1 (named swo1-w1), the gene coding for chaperone Hsp90, which is required to stabilise Wee1. The swo1-w1 allele carries a glycine to aspartic acid substitution at amino acid 155 that results in a partial loss of Hsp90 function. Cells bearing the swo1-w1 mutation in combination with the point mutation cdc2-33 or cdc2-M26 showed severe mitotic defects. Genetic interactions were not observed in combination with point mutations in other cdc genes, suggesting that Cdc2 specifically interacts with Hsp90. This synthetic lethal swo1-w1 cdc2-33 (or cdc2-M26) strain had normal levels of Cdc2 protein and histone H1 phosphorylation activity, indicating that Hsp90 is required to enable Cdc2 to interact with its mitotic substrates or regulators, rather than for its proper folding or stabilisation. In a wild-type background, swo1-w1 mutant cells were sensitive to temperature as well as to other stress agents, such as KCl, ethanol and formamide. Under these stressful growth conditions, the swo1-w1 cells displayed anapbase B arrest and aberrant septation patterns, indicating that a subset of proteins involved in mitosis and cytokinesis is highly dependent on chaperone Hsp90 for function.
引用
收藏
页码:242 / 250
页数:9
相关论文
共 42 条
  • [1] AGUILERA A, 1994, GENETICS, V136, P87
  • [2] Alfa C., 1993, EXPT FISSION YEAST L
  • [3] A ROLE FOR HSP90 IN CELL-CYCLE CONTROL - WEE1 TYROSINE KINASE-ACTIVITY REQUIRES INTERACTION WITH HSP90
    ALIGUE, R
    AKHAVANNIAK, H
    RUSSELL, P
    [J]. EMBO JOURNAL, 1994, 13 (24) : 6099 - 6106
  • [4] Chaperone function of Hsp90-associated proteins
    Bose, S
    Weikl, T
    Bugl, H
    Buchner, J
    [J]. SCIENCE, 1996, 274 (5293) : 1715 - 1717
  • [5] BROEK D, 1991, NATURE, V349, P388, DOI 10.1038/349388a0
  • [6] FINISHING THE CELL-CYCLE - CONTROL OF MITOSIS AND CYTOKINESIS IN FISSION YEAST
    CHANG, F
    NURSE, P
    [J]. TRENDS IN GENETICS, 1993, 9 (10) : 333 - 335
  • [7] Chen CF, 1996, MOL CELL BIOL, V16, P4691
  • [8] Physical interaction of mammalian CDC37 with CDK4
    Dai, K
    Kobayashi, R
    Beach, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (36) : 22030 - 22034
  • [9] The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperone cofactors
    Demand, J
    Lüders, J
    Höhfeld, J
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (04) : 2023 - 2028
  • [10] Reconstitution of the steroid receptor center dot hsp90 heterocomplex assembly system of rabbit reticulocyte lysate
    Dittmar, KD
    Hutchison, KA
    OwensGrillo, JK
    Pratt, WB
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (22) : 12833 - 12839