UNC45A定位于中心体，并通过激活ChK1来调节癌细胞增殖。
UNC45A localizes to centrosomes and regulates cancer cell proliferation through ChK1 activation.
作者信息
Jilani Yasmeen, Lu Su, Lei Huang, Karnitz Larry M, Chadli Ahmed
机构信息
Molecular Oncology and Biomarkers Program, GRU Cancer Center, Georgia Regents University, 1410 Laney Walker Blvd, CN-3151, Augusta, GA 30912, USA.
Cancer Immunology, Inflammation, and Tolerance Program, Georgia Regents University Cancer Center, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912.
出版信息
Cancer Lett. 2015 Feb 1;357(1):114-120. doi: 10.1016/j.canlet.2014.11.009. Epub 2014 Nov 10.
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.
UCS蛋白家族通过与肌球蛋白相互作用来调节细胞功能。在此我们表明，该家族的一个成员UNC45A也是一种新型的中心体蛋白。UNC45A通过其以不依赖Hsp90的方式结合并调节ChK1核质定位的能力，在体外对癌细胞的增殖以及在体内对肿瘤生长是必需的。免疫细胞化学和生化分级分离研究表明，UNC45A和ChK1共定位于中心体。抑制UNC45A的表达会降低ChK1的激活及其与中心体的栓系，而这些是中心体正常功能所需的事件。缺乏UNC45A会导致多核细胞的积累，这与Chk1对中心体调节的缺陷一致。这些发现确定了UNC45A的一种新型中心体功能及其在细胞增殖和肿瘤发生中的作用。
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