title: The topoisomerase I-binding RING protein, topors, is associated with promyelocytic leukemia nuclear bodies.
abstract: We previously identified topors as a topoisomerase I-binding protein that localizes in punctate nuclear regions when expressed as a GFP fusion protein. We now demonstrate that both the GFP-topors fusion protein and endogenous topors are associated with promyelocytic leukemia (PML) nuclear bodies in exponentially growing HeLa cells. Studies using isogenic PML+/+ and PML-/- murine embryonic fibroblasts indicate that the punctate nuclear localization of topors is dependent on PML. A basic C-terminal region but not the N-terminal RING domain of topors is required for the punctate nuclear localization of this protein. Additional studies indicate that topors, but not PML, rapidly relocalizes from nuclear bodies to the nucleoplasm in cells exposed to the transcription inhibitor dichloro-1-beta-d-ribofuranolsylbenzimidazole or to the topoisomerase I-targeting drug camptothecin. These results identify topors as a new member of the group of proteins that associate dynamically with PML nuclear bodies and suggest that topors may be involved in the cellular response to camptothecin.
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-2681, USA.
authors.forename: Zeshaan A
authors.initials: ZA
authors.lastname: Rasheed
authors.forename: Ahamed
authors.initials: A
authors.lastname: Saleem
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Ravee
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.forename: Eric H
authors.initials: EH
authors.lastname: Rubin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002166:Camptothecin / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002874:Chromosome Mapping; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D000071156:Promyelocytic Leukemia Protein; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D059004:Topoisomerase I Inhibitors; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D011993:Recombinant Fusion Proteins; D059004:Topoisomerase I Inhibitors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D004004:Dichlororibofuranosylbenzimidazole; C120157:TOPORS protein, human; D044767:Ubiquitin-Protein Ligases; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin; D004121:Dimethyl Sulfoxide