UNC45A localizes to centrosomes and regulates cancer cell proliferation through ChK1 activation

Abstract

The UCS family of proteins regulates cellular functions through their interactions with myosin. Here we show that one member of this family, UNC45A, is also a novel centrosomal protein. UNC45A is required for cellular proliferation of cancer cell in vitro and for tumor growth in vivo through its ability to bind and regulate ChK1 nuclear-cytoplasmic localization in an Hsp90-independent manner. Immunocytochemical and biochemical fractionation studies revealed that UNC45A and ChK1 co-localize to the centrosome. Inhibition of UNC45A expression reduced ChK1 activation and its tethering to the centrosome, events required for proper centrosome function. Lack of UNC45A caused the accumulation of multi-nucleated cells, consistent with a defect in Chk1 regulation of centrosomes. These findings identify a novel centrosomal function for UNC45A and its role in cell proliferation and tumorigenesis.

Keywords: Centrosome; ChK1; Chaperone; Hsp90; Tumorigenesis; UNC45A.