The myxoid liposarcoma specific TLS-CHOP fusion protein localizes to nuclear structures distinct from PML nuclear bodies

Int J Cancer. 2002 Feb 1;97(4):446-50. doi: 10.1002/ijc.1632.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • COS Cells
  • Cell Division
  • Cell Fractionation
  • Cell Nucleus / chemistry*
  • 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 / genetics*
  • Liposarcoma, Myxoid / ultrastructure
  • Luminescent Proteins / analysis
  • Luminescent Proteins / genetics
  • Neoplasm Proteins / analysis
  • Nuclear Proteins*
  • Oncogene Proteins, Fusion / metabolism*
  • Polymerase Chain Reaction
  • Proliferating Cell Nuclear Antigen / analysis
  • Promyelocytic Leukemia Protein
  • RNA-Binding Protein FUS*
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factor CHOP
  • Transcription Factors / analysis
  • Transfection
  • Translocation, Genetic
  • Tumor Suppressor Proteins

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Ki-67 Antigen
  • Luminescent Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Proliferating Cell Nuclear Antigen
  • Promyelocytic Leukemia Protein
  • RNA-Binding Protein FUS
  • Recombinant Fusion Proteins
  • TLS-CHOP fusion protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Transcription Factor CHOP
  • Green Fluorescent Proteins