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Gene Review

wee1  -  M phase inhibitor protein kinase Wee1

Schizosaccharomyces pombe 972h-

 
 
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High impact information on wee1

 

Biological context of wee1

  • Mitotic delay in response to DNA damage is thus distinct from the delay induced by inhibition of DNA synthesis, which involves cdc25 but is not dependent on wee1 [3].
  • Finally, the characteristic suppression of the cdc25 phenotype by a loss-of-function wee1 mutation is reversed in a mcs3 mutant background [4].
  • Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog [5].
  • The carboxy-terminal region of the predicted 112 kd wee1+ protein contains protein kinase consensus sequences, suggesting that negative regulation of mitosis involves protein phosphorylation [5].
  • Fifty-one of the mutants map at the wee1 locus, which is unlinked to any known cdc gene [6].
 

Anatomical context of wee1

 

Associations of wee1 with chemical compounds

  • The nutritional size control and its major known controlling elements, the wee1/mik1 protein kinases, and cdc25 protein tyrosine phosphatase are considered in detail along with their regulation [9].
  • For wee1 mutant cells of Schizosaccharomyces pombe the DNA-division sequence of the cell cycle can be differentially slowed by the presence of low concentrations of the S-phase inhibitor hydroxyurea, or by semipermissive temperatures for certain wee1 cdc double mutants [10].
 

Regulatory relationships of wee1

  • Genetic evidence indicates that wee1+ and cdc25+ compete in a control system regulating the cdc2+ protein kinase, which is required for mitotic initiation [5].
  • Previous studies suggest that overexpression of pyp1+ results in a mitotic delay by positively regulating wee1 activity [11].
  • The presence of a wee1 mutation phenotypically suppresses cdc25 mutations [12].
 

Other interactions of wee1

  • The simplest interpretation of these observations is that wee1+ codes for a negative element or inhibitor, and cdc2+ codes for a positive element or activator in the mitotic control [6].
  • Overexpression of pyp1 or pyp2 delays the onset of mitosis by a wee1-dependent mechanism [13].
  • Cells bearing inactive wee1 are unresponsive to disruption of pyp1 [13].
  • Further, wee1 is required for cell cycle arrest induced by up-regulation of an essential component of this checkpoint, chk1 [14].
  • It was isolated by virtue of its interaction with the mitotic control genes cdc25, wee1 and win1 [15].
 

Analytical, diagnostic and therapeutic context of wee1

  • Using flow cytometry and a double-block experiment, we have measured the position of this transition point both in the single mutant and in the double mutant cdc2.33 wee1 [16].

References

  1. Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer. Coleman, T.R., Tang, Z., Dunphy, W.G. Cell (1993) [Pubmed]
  2. Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. Heald, R., McLoughlin, M., McKeon, F. Cell (1993) [Pubmed]
  3. The wee1 protein kinase is required for radiation-induced mitotic delay. Rowley, R., Hudson, J., Young, P.G. Nature (1992) [Pubmed]
  4. cdc2 and the regulation of mitosis: six interacting mcs genes. Molz, L., Booher, R., Young, P., Beach, D. Genetics (1989) [Pubmed]
  5. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Russell, P., Nurse, P. Cell (1987) [Pubmed]
  6. Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Nurse, P., Thuriaux, P. Genetics (1980) [Pubmed]
  7. A protein phosphatase 1 from Arabidopsis thaliana restores temperature sensitivity of a Schizosaccharomyces pombe cdc25ts/wee1- double mutant. Ferreira, P.C., Hemerly, A.S., Van Montagu, M., Inzé, D. Plant J. (1993) [Pubmed]
  8. Genetic interactions between Hsp90 and the Cdc2 mitotic machinery in the fission yeast Schizosaccharomyces pombe. Muñoz, M.J., Jimenez, J. Mol. Gen. Genet. (1999) [Pubmed]
  9. Regulation of the G2-mitosis transition. Feilotter, H., Lingner, C., Rowley, R., Young, P.G. Biochem. Cell Biol. (1992) [Pubmed]
  10. Novel cell cycle regulation in the yeast Schizosaccharomyces pombe. The DNA-division sequence modulates mass accumulation. Johnston, G.C., Singer, R.A. Exp. Cell Res. (1985) [Pubmed]
  11. The Schizosaccharomyces pombe pyp1 protein tyrosine phosphatase negatively regulates nutrient monitoring pathways. Dal Santo, P., Blanchard, B., Hoffman, C.S. J. Cell. Sci. (1996) [Pubmed]
  12. Isolation of a novel type of mutation in the mitotic control of Schizosaccharomyces pombe whose phenotypic expression is dependent on the genetic background and nutritional environment. Ogden, J.E., Fantes, P.A. Curr. Genet. (1986) [Pubmed]
  13. Negative regulation of mitosis by two functionally overlapping PTPases in fission yeast. Millar, J.B., Russell, P., Dixon, J.E., Guan, K.L. EMBO J. (1992) [Pubmed]
  14. Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation. O'Connell, M.J., Raleigh, J.M., Verkade, H.M., Nurse, P. EMBO J. (1997) [Pubmed]
  15. The wis1 protein kinase is a dosage-dependent regulator of mitosis in Schizosaccharomyces pombe. Warbrick, E., Fantes, P.A. EMBO J. (1991) [Pubmed]
  16. The first transition point of the mutant cdc2.33 in the fission yeast Schizosaccharomyces pombe. Novak, B., Mitchison, J.M. J. Cell. Sci. (1989) [Pubmed]
 
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