P53, cyclin-dependent kinase and abnormal amplification of centrosomes.
Centrosomes play a critical role in formation of bipolar mitotic spindles, an essential event for accurate chromosome segregation into daughter cells. Numeral abnormalities of centrosomes (centrosome amplification) occur frequently in cancers, and are considered to be the major cause of chromosome instability, which accelerates acquisition of malignant phenotypes during tumor progression. Loss or mutational inactivation of p53 tumor suppressor protein, one of the most common mutations found in cancers, results in a high frequency of centrosome amplification in part via allowing the activation of the cyclin-dependent kinase (CDK) 2-cyclin E (as well as CDK2-cyclin A) which is a key factor for the initiation of centrosome duplication. In this review, the role of centrosome amplification in tumor progression, and mechanistic view of how centrosomes are amplified in cells through focusing on loss of p53 and aberrant activities of CDK2-cyclins will be discussed.
Fukasawa
Kenji
K
Molecular Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. kenji.fukasawa@moffitt.org
D000818:Animals; D018385:Centrosome / Q000502:physiology*; D019927:Cyclin E / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2 / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D008941:Spindle Apparatus / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D019927:Cyclin E; D016159:Tumor Suppressor Protein p53; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases