title: 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.
authors.affiliation: Molecular Oncology and Biomarkers Program, GRU Cancer Center, Georgia Regents University, 1410 Laney Walker Blvd, CN-3151, Augusta, GA 30912, USA.
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Jilani
authors.affiliation: Molecular Oncology and Biomarkers Program, GRU Cancer Center, Georgia Regents University, 1410 Laney Walker Blvd, CN-3151, Augusta, GA 30912, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Lu
authors.affiliation: Cancer Immunology, Inflammation, and Tolerance Program, Georgia Regents University Cancer Center, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912.
authors.forename: Huang
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Larry M
authors.initials: LM
authors.lastname: Karnitz
authors.affiliation: Molecular Oncology and Biomarkers Program, GRU Cancer Center, Georgia Regents University, 1410 Laney Walker Blvd, CN-3151, Augusta, GA 30912, USA. Electronic address: achadli@gru.edu.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Chadli
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D018385:Centrosome / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; C509158:UNC45A protein, human; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1
keywords: Centrosome; ChK1; Chaperone; Hsp90; Tumorigenesis; UNC45A