STK15/BTAK and Centrosome Anomaly in Human Breast Cancer

摘要

STK15/BTAk is a member of the Aurora/Ipll related serine/threonine kinase super family that is associated with centrosomes, exhibits elevated expression in many human cancers. Ectopic over expression of this kinase induces aneuploidy, centrosome amplification and tumorigenic transformation in cells grown in vitro. In the study conduced during this funded project, the findings are the following: (a) The familial breast cancer susceptibility gene BRCA1, which co-localizes to centrosome during mitosis, interacts with STK15 in vivo and is phosphorylated by STK15 kinase immunoprecipitated from mitotic cells in in vitro kinase assays. W have mapped the STK15 binding domain on BRCA and have mapped the putative STK15 phosphorylation site on BRCA1. (b) The tumor suppressor protein p53, which localizes to centrosome is phosphorylated by STK15 and this phosphorylation leads to destabilization and inhibition of p53. (c) The central peptide domain of STK15 unnecessary for localization of this protein kinase to the centrosomes. Centrosome localization of STK15 is augmented by sequences of both the amino and the carboxy terminal ends of the protein.