Abstract
Human myxoid liposarcomas contain a characteristic chromosomal translocation, t(12;16)(q13;p11), that is associated with a structural rearrangement of the gene encoding CHOP, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors residing on 12q13.1. Using a CHOP-specific complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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CCAAT-Enhancer-Binding Proteins*
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Cell Line
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Chromosomes, Human, Pair 12
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Chromosomes, Human, Pair 16
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Cloning, Molecular
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DNA, Neoplasm
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DNA-Binding Proteins / genetics*
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Escherichia coli
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HeLa Cells
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Heterogeneous-Nuclear Ribonucleoproteins
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Humans
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Liposarcoma / genetics*
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Mice
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Molecular Sequence Data
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Neoplasm Proteins / genetics*
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Nuclear Proteins / genetics*
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Protein Multimerization
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RNA-Binding Protein EWS
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RNA-Binding Protein FUS
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RNA-Binding Proteins / genetics*
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Ribonucleoproteins / genetics*
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Sequence Homology, Amino Acid
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Transcription Factor CHOP
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Transcription Factors*
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Transfection
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Translocation, Genetic
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Tumor Cells, Cultured
Substances
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CCAAT-Enhancer-Binding Proteins
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DDIT3 protein, human
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DNA, Neoplasm
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DNA-Binding Proteins
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Ddit3 protein, mouse
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Heterogeneous-Nuclear Ribonucleoproteins
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Neoplasm Proteins
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Nuclear Proteins
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RNA-Binding Protein EWS
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RNA-Binding Protein FUS
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RNA-Binding Proteins
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Ribonucleoproteins
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Transcription Factors
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Transcription Factor CHOP