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WEE1  -  WEE1 G2 checkpoint kinase

Homo sapiens

Synonyms: WEE1A, WEE1hu, Wee1-like protein kinase, Wee1A kinase
 
 
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High impact information on WEE1

  • Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase [1].
  • The human WEE1 kinase phosphorylated the p34cdc2-cyclin B complex on tyrosine 15 but not on threonine 14 in vitro and inactivated the p34cdc2-cyclin B kinase [1].
  • Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates, hence it is likely to have an important role in the mitotic control of human cells [2].
  • Cell cycle regulation of human WEE1 [2].
  • WEE1 activity was not found to be elevated in HeLa cells arrested in S phase, suggesting that unreplicated DNA does not delay M phase by hyperactivating WEE1 [2].
 

Biological context of WEE1

  • M phase WEE1 is re-activated in samples prepared in the absence of protein phosphatase inhibitors, demonstrating that WEE1 is inhibited by a mechanism that requires protein phosphorylation [2].
  • Taken together, these results indicate that the original WEE1Hu clone isolated in genetic screens encodes only the catalytic domain of human WEE1 and that the authentic human WEE1 protein has an apparent molecular mass of approximately 95 kDa [3].
  • Inhibition of p34cdc2 activity by transient overexpression of a dominant-negative cdc2 construct or human WEE1 kinase inhibited Fas-mediated apoptosis [4].
  • In addition, we demonstrated that Wee1 expression prevents cancer cells from undergoing apoptosis in response to DNA damage; however, this resistance was abolished by coexpression of KLF2, which inhibits WEE1 transcription [5].
  • In the pluteus larva of the species Lytechinus pictus, WEE1 mRNA was detected in the arm rudiments during cellular proliferation and arm elongation, but not after the completion of the arms [6].
 

Anatomical context of WEE1

  • Human WEE1 kinase isolated from unirradiated or irradiated leukemic B-cell precursors had minimal tyrosine kinase activity towards p34cdc2 [7].
  • Construction and co-expression of bicistronic plasmid encoding human WEE1 and stem cell factor [8].
 

Regulatory relationships of WEE1

  • Thus, the level of WEE1 is regulated by KLF2 and enhanced KLF2 expression sensitizes cells to DNA damage-induced apoptosis [5].
 

Other interactions of WEE1

 

Analytical, diagnostic and therapeutic context of WEE1

References

  1. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Parker, L.L., Piwnica-Worms, H. Science (1992) [Pubmed]
  2. Cell cycle regulation of human WEE1. McGowan, C.H., Russell, P. EMBO J. (1995) [Pubmed]
  3. Identification of a 95-kDa WEE1-like tyrosine kinase in HeLa cells. Parker, L.L., Sylvestre, P.J., Byrnes, M.J., Liu, F., Piwnica-Worms, H. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. Requirement of p34cdc2 kinase for apoptosis mediated by the Fas/APO-1 receptor and interleukin 1beta-converting enzyme-related proteases. Yao, S.L., McKenna, K.A., Sharkis, S.J., Bedi, A. Cancer Res. (1996) [Pubmed]
  5. Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis. Wang, F., Zhu, Y., Huang, Y., McAvoy, S., Johnson, W.B., Cheung, T.H., Chung, T.K., Lo, K.W., Yim, S.F., Yu, M.M., Ngan, H.Y., Wong, Y.F., Smith, D.I. Oncogene (2005) [Pubmed]
  6. WEE1-like CDK tyrosine kinase mRNA level is regulated temporally and spatially in sea urchin embryos. Nemer, M., Stuebing, E.W. Mech. Dev. (1996) [Pubmed]
  7. Role of tyrosine phosphorylation in radiation-induced cell cycle-arrest of leukemic B-cell precursors at the G2-M transition checkpoint. Tuel-Ahlgren, L., Jun, X., Waddick, K.G., Jin, J., Bolen, J., Uckun, F.M. Leuk. Lymphoma (1996) [Pubmed]
  8. Construction and co-expression of bicistronic plasmid encoding human WEE1 and stem cell factor. Lei, P., Li, W.H., Liao, W.J., Yu, B., Zhu, H.F., Shao, J.F., Shen, G.X. Acta Biochim. Biophys. Sin. (Shanghai) (2005) [Pubmed]
  9. Wild-type TP53 inhibits G(2)-phase checkpoint abrogation and radiosensitization induced by PD0166285, a WEE1 kinase inhibitor. Li, J., Wang, Y., Sun, Y., Lawrence, T.S. Radiat. Res. (2002) [Pubmed]
  10. Localization of human cell cycle regulatory genes CDC25C to 5q31 and WEE1 to 11p15.3-11p15.1 by fluorescence in situ hybridization. Taviaux, S.A., Demaille, J.G. Genomics (1993) [Pubmed]
  11. Comparative architectural aspects of regions of conserved synteny on human chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1). Cichutek, A., Brueckmann, T., Seipel, B., Hauser, H., Schlaubitz, S., Prawitt, D., Hankeln, T., Schmidt, E.R., Winterpacht, A., Zabel, B.U. Cytogenet. Cell Genet. (2001) [Pubmed]
  12. Circadian clock coordinates cancer cell cycle progression, thymidylate synthase, and 5-fluorouracil therapeutic index. Wood, P.A., Du-Quiton, J., You, S., Hrushesky, W.J. Mol. Cancer Ther. (2006) [Pubmed]
 
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