title: Characterization of nuclear localization and SUMOylation of the ATBF1 transcription factor in epithelial cells.
abstract: ATBF1/ZFHX3 is a large transcription factor that functions in development, tumorigenesis and other biological processes. ATBF1 is normally localized in the nucleus, but is often mislocalized in the cytoplasm in cancer cells. The mechanism underlying the mislocalization of ATBF1 is unknown. In this study, we analyzed the nuclear localization of ATBF1, and found that ectopically expressed ATBF1 formed nuclear body (NB)-like dots in the nucleus, some of which indeed physically associated with promyelocytic leukemia (PML) NBs. We also defined a 3-amino acid motif, KRK2615-2617, as the nuclear localization signal (NLS) for ATBF1. Interestingly, diffusely distributed nuclear SUMO1 proteins were sequestered into ATBF1 dots, which could be related to ATBF1's physical association with PML NBs, known SUMOylation hotspots. Furthermore, ATBF1 itself was SUMOylated. ATBF1 SUMOylation occurred at more than 3 lysine residues including K2349, K2806 and K3258 and was nuclear specific. Finally, the PIAS3 SUMO1 E3 ligase, which interacts with ATBF1 directly, diminished rather than enhanced ATBF1 SUMOylation, preventing the co-localization of ATBF1 with SUMO1 in the nucleus. These findings suggest that nuclear localization and SUMOylation are important for the transcription factor function of ATBF1, and that ATBF1 could cooperate with PML NBs to regulate protein SUMOylation in different biological processes.
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Frederick N
authors.initials: FN
authors.lastname: Dong
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D021381:Protein Transport; D025842:SUMO-1 Protein / Q000378:metabolism; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D018832:Molecular Chaperones; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; C484745:PIAS3 protein, human; D000071156:Promyelocytic Leukemia Protein; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C071660:ZFHX3 protein, human; D008239:Lysine