title: The myxoid liposarcoma specific TLS-CHOP fusion protein localizes to nuclear structures distinct from PML nuclear bodies.
abstract: CHOP in 12q13, also called GADD153 or DDIT3, encodes a transcription factor of the C/EBP type. As a result of t(12;16) translocations, CHOP is rearranged and fused to TLS in 16p11 in about 90% of myxoid liposarcomas/round cell liposarcomas (MLS/RCLS). The TLS-CHOP protein consists of the N-terminal half of TLS juxtaposed to the N-terminal of the entire CHOP. It is capable of forming dimers with the natural dimer partners of CHOP. Here we report that recombinant TLS-CHOP-green fluorescence protein localizes to nuclear structures, similar to, but distinct from, PML nuclear bodies. The TLS-CHOP-green fluorescent protein nuclear structures are resistant to high salt concentration and nuclease treatment. Transfection of TLS-CHOP to normal fibroblasts causes a rapid down regulation and relocation of PML nuclear bodies. An abnormal extra nuclear localization of PML bodies was also found in TLS-CHOP carrying cell lines established from myxoid liposarcomas. Transfection of TLS-CHOP induced a rapid disappearance of PCNA. TLS-CHOP may disturb the nuclear machinery by binding and sequestering important factors from their natural sites.
authors.affiliation: The Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Gothenburg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Thelin-Järnum
authors.forename: Melker
authors.initials: M
authors.lastname: Göransson
authors.forename: Alondra Schweizer
authors.initials: AS
authors.lastname: Burguete
authors.forename: Anita
authors.initials: A
authors.lastname: Olofsson
authors.forename: Pierre
authors.initials: P
authors.lastname: Aman
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D019556:COS Cells; D002455:Cell Division; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000737:chemistry* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics / Q000648:ultrastructure; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry; D019281:Dimerization; D005347:Fibroblasts / Q000378:metabolism; D005354:Fibrosarcoma / Q000473:pathology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D018208:Liposarcoma, Myxoid / Q000235:genetics* / Q000648:ultrastructure; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D000071156:Promyelocytic Leukemia Protein; D034702:RNA-Binding Protein FUS; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000032:analysis; D014162:Transfection; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D019394:Ki-67 Antigen; D008164:Luminescent Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D018809:Proliferating Cell Nuclear Antigen; D000071156:Promyelocytic Leukemia Protein; D034702:RNA-Binding Protein FUS; D011993:Recombinant Fusion Proteins; C106030:TLS-CHOP fusion protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D051742:Transcription Factor CHOP; D049452:Green Fluorescent Proteins