Charakterisierung und funktionelle Analyse der Interaktion zwischen Polo-like Kinase 1 und mitotischem Zentromer-assoziierten Kinesin

• Applicant: Professorin Dr. Juping Yuan
• Subject Area: Gynaecology and Obstetrics
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 188052775

• Final Report Year: 2015

Final Report Abstract

In summary, our observations have greatly contributed to the molecular mechanism by which the mitotic kinase Plk1 regulates MCAK. Overexpression of Plk1, observed in various human tumors, contributes greatly to the deregulated MCAK, leading further to genome instability and abnormal microtubule dynamics, which could subsequently modulate the cytoskeleton and mobility, and promote invasion, metastasis and therapy resistance of tumor cells. Further investigations are currently ongoing to address these issues.

Publications

• Mitotic centromere-associated kinesin (MCAK): a potential cancer drug target. Oncotarget 2011, 2(12):935-47
  Sanhaji M, Friel CT, Wordeman L, Louwen F, Yuan J
  
• Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells. Nat Commun. 2011, 2:395
  Raab M, Kappel S, Krämer A, Sanhaji M, Matthess Y, Kurunci-Csacsko E, Calzada- Wack J, Rathkolb B, Rozman J, Adler T, Busch DH, Esposito I, Fuchs H, Gailus-Durner V, Klingenspor M, Wolf E, Sänger N, Prinz F, Angelis MH, Seibler J, Yuan J, Bergmann M, Knecht R, Kreft B, Strebhardt K
  
• p53 is not directly relevant to the response of Polo-like kinase 1 inhibitors. Cell Cycle 2012, 11(3):543-53
  Sanhaji M, Kreis NN, Zimmer B, Berg T, Louwen F, Yuan J
  (See online at https://doi.org/10.4161/cc.11.3.19076)
• Polo-like kinase 1 inhibitors, mitotic stress and the tumor suppressor p53. Cell Cycle 2013, 12(9):1340- 5110
  Sanhaji M, Louwen F, Zimmer B, Kreis NN, Roth S, Yuan J
  (See online at https://doi.org/10.4161/cc.24573)
• p21Waf1/Cip1 deficiency causes multiple mitotic defects in tumor cells. Oncogene 2014, 33(50):5716-28
  Kreis NN, Sanhaji M, Rieger MA, Louwen F and Yuan J
  (See online at https://doi.org/10.1038/onc.2013.518)
• Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis. Oncotarget 2014, 5(10):3130-44
  Sanhaji M, Ritter A, Belsham HR, Friel CT, Roth S, Louwen F and Yuan J
  (See online at https://doi.org/10.18632/oncotarget.1861)
• The activity regulation of the mitotic centromere-associated kinesin by Polo-like kinase 1. Oncotarget 2014 Dec 2. [Epub ahead of print]
  Ritter A, Sanhaji M, Steinhäuser K, Roth S, Louwen F, Yuan J
  (See online at https://doi.org/10.18632/oncotarget.2843)
• Mitotic arrest and slippage induced by pharmacological inhibition of Polo-like kinase 1. Mol Oncol. 2015, 9(1):140-54
  Raab M, Krämer A, Hehlgans S, Sanhaji M, Kurunci-Csacsko E, Dötsch C, Bug G, Ottmann O, Becker S, Pachl F, Kuster B, Strebhardt K
  (See online at https://doi.org/10.1016/j.molonc.2014.07.020)