| Popis: |
Numeral abnormality of centrosomes (presence of more than two centrosomes) leads to mitotic defects and high frequencies of chromosome segregation errors. Centrosome amplification occurs frequently in various types of human cancers, and is believed to be a major cause of chromosomal instability. Centrosome amplification in many cases results from over-duplication (more than one duplication in a single cell cycle) caused by aberrant activities of the positive and negative regulators of centrosome duplication. Centrosome duplication is triggered by the cyclin-dependent kinase 2 (CDK2)-cyclin E kinase complex through targeting several centrosomally localized proteins, including Mps1 kinase. In contrast, p53 tumor suppressor protein suppresses centrosome duplication partly through transactivating p21 CDK inhibitor, and partly through direct regulation at centrosomes. Mortalin localizes to centrosomes, and when overexpressed, promotes centrosome duplication and induces centrosome amplification via targeting both Mps1 and p53. Here, we discuss the involvement of mortalin in the regulation of centrosome duplication and re-duplication, revealing a new and important aspect of oncogenic activity of mortalin, namely induction of numeral abnormality of centrosomes and consequent chromosome instability. |
