title: The centrosome and mitotic spindle apparatus in cancer and senescence.
abstract: Altered cell division is associated with overproliferation and tumorigenesis, however, mitotic aberrations can also trigger antiproliferative responses leading to postmitotic cell cycle exit. Here, we focus on the role of the centrosome and in particular of centrosomal TACC (transforming acidic coiled coil) proteins in tumorigenesis and cellular senescence. We have complied recent evidence that inhibition or depletion of various mitotic proteins which take over key in centrosome and kinetochore integrity and mitotic checkpoint function in sufficient to activate a p53-p21(WAF) driven premature senescence phenotype. These findings have direct implications for proliferative tissue homeostasis as well as for cellular and organismal aging.
authors.affiliation: Institut für Biochemie und Molekularbiologie II, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Schmidt
authors.forename: Frank
authors.initials: F
authors.lastname: Essmann
authors.forename: Ion C
authors.initials: IC
authors.lastname: Cirstea
authors.forename: Fabian
authors.initials: F
authors.lastname: Kuck
authors.forename: Harish C
authors.initials: HC
authors.lastname: Thakur
authors.forename: Madhurendra
authors.initials: M
authors.lastname: Singh
authors.forename: Anja
authors.initials: A
authors.lastname: Kletke
authors.forename: Reiner U
authors.initials: RU
authors.lastname: Jänicke
authors.forename: Constanze
authors.initials: C
authors.lastname: Wiek
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: M Reza
authors.initials: MR
authors.lastname: Ahmadian
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Bernd
authors.initials: B
authors.lastname: Nürnberg
authors.forename: Roland P
authors.initials: RP
authors.lastname: Piekorz
mesh_terms: D064127:Aurora Kinases; D049109:Cell Proliferation; D016922:Cellular Senescence; D018385:Centrosome / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology; D008938:Mitosis; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D008869:Microtubule-Associated Proteins; D016159:Tumor Suppressor Protein p53; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases