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

Open Access
Publisher Website
Google Scholar
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.
Funding Information
  • Swedish Cancer Society
  • Children′s Cancer Society
  • King Gustav V Jubilee Clinic Cancer Research Foundation
  • Assar Gabrielssons Foundation
  • Medical Faculty of Göteborg University