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Int J Cancer ; 97(4): 446-50, 2002 Feb 01.
Article in English | MEDLINE | ID: mdl-11802205

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.


Subject(s)
CCAAT-Enhancer-Binding Proteins/metabolism , Cell Nucleus/chemistry , Liposarcoma, Myxoid/genetics , Nuclear Proteins , Oncogene Proteins, Fusion/metabolism , RNA-Binding Protein FUS , Animals , COS Cells , Cell Division , Cell Fractionation , Cell Nucleus/ultrastructure , Chlorocebus aethiops , Chromosomes, Human, Pair 12/genetics , Chromosomes, Human, Pair 12/ultrastructure , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 16/ultrastructure , Cytoplasm/chemistry , Dimerization , Fibroblasts/metabolism , Fibrosarcoma/pathology , Genes, Reporter , Green Fluorescent Proteins , Humans , Ki-67 Antigen/analysis , Leukemia, Promyelocytic, Acute/genetics , Liposarcoma, Myxoid/ultrastructure , Luminescent Proteins/analysis , Luminescent Proteins/genetics , Neoplasm Proteins/analysis , Polymerase Chain Reaction , Proliferating Cell Nuclear Antigen/analysis , Promyelocytic Leukemia Protein , Recombinant Fusion Proteins/metabolism , Transcription Factor CHOP , Transcription Factors/analysis , Transfection , Translocation, Genetic , Tumor Suppressor Proteins
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