Hsp90 chaperone complexes are required for the activity and stability of yeast protein kinases Mik1, Wee1 and Swe1

被引:57
作者
Goes, FS [1 ]
Martin, J [1 ]
机构
[1] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 2001年 / 268卷 / 08期
关键词
cell cycle; chaperones; Hsp90; protein kinase; yeast;
D O I
10.1046/j.1432-1327.2001.02105.x
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
The Wee1 protein kinase negatively regulates entry into mitosis by mediating the inhibitory tyrosine phosphorylation of Cdc2-cyclin B kinase. The stability and activity of Wee1 from the fission yeast Schizosaccharomyces pombe is critically dependent on functional Hsp90 chaperones. Here we identify two related tyrosine protein kinases, Mik1 from fission yeast and its Saccharomyces cerevisiae homolog Swe1, as Hsp90 substrates and show that the kinase domain is sufficient to mediate this interaction. Morphological and biochemical defects arising from overexpression of the kinases in fission yeast are suppressed in the conditional Hsp90 mutant swo1-26. A subset of all three kinases is associated with the Hsp90 cochaperones cyclophilin 40 and p23. Under conditions of impaired chaperone function or treatment with the Hsp90 inhibitory drug geldanamycin, intracellular levels of the kinases are reduced and the proteins become rapidly degraded by the proteasome machinery, indicating that Wee1, Mik1 and Swe1 require Hsp90 heterocomplexes for their stability and maintenance of function.
引用
收藏
页码:2281 / 2289
页数:9
相关论文
共 50 条
[1]  
Alfa C., 1993, EXPT FISSION YEAST L
[2]  
ALFA CE, 1991, COLD SPRING HARB SYM, V56, P489
[3]   A ROLE FOR HSP90 IN CELL-CYCLE CONTROL - WEE1 TYROSINE KINASE-ACTIVITY REQUIRES INTERACTION WITH HSP90 [J].
ALIGUE, R ;
AKHAVANNIAK, H ;
RUSSELL, P .
EMBO JOURNAL, 1994, 13 (24) :6099-6106
[4]   Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase [J].
Aligue, R ;
Wu, L ;
Russell, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (20) :13320-13325
[5]   TATA BOX MUTATIONS IN THE SCHIZOSACCHAROMYCES-POMBE NMT-1 PROMOTER AFFECT TRANSCRIPTION EFFICIENCY BUT NOT THE TRANSCRIPTION START POINT OR THIAMINE REPRESSIBILITY [J].
BASI, G ;
SCHMID, E ;
MAUNDRELL, K .
GENE, 1993, 123 (01) :131-136
[6]   Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function of Hsp90-dependent signaling proteins [J].
Bohen, SP .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (06) :3330-3339
[7]   PROPERTIES OF SACCHAROMYCES-CEREVISIAE WEE1 AND ITS DIFFERENTIAL REGULATION OF P34(CDC28) IN RESPONSE TO G(1) AND G(2) CYCLINS [J].
BOOHER, RN ;
DESHAIES, RJ ;
KIRSCHNER, MW .
EMBO JOURNAL, 1993, 12 (09) :3417-3426
[8]   Hsp90's secrets unfold: new insights from structural and functional studies [J].
Caplan, AJ .
TRENDS IN CELL BIOLOGY, 1999, 9 (07) :262-268
[9]   CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that suppresses cyclophilin 40 mutations and interacts with Hsp90 [J].
Dolinski, KJ ;
Cardenas, ME ;
Heitman, J .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (12) :7344-7352
[10]   Hsp90 binds and regulates the ligand-inducible α subunit of eukaryotic translation initiation factor kinase Gcn2 [J].
Donzé, O ;
Picard, D .
MOLECULAR AND CELLULAR BIOLOGY, 1999, 19 (12) :8422-8432