Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.
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.
Department of Medicine, NYU Medical Center, New York 10016.
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Crozat
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Aman
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Mandahl
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Ron
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D002881:Chromosomes, Human, Pair 12; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000235:genetics*; D004926:Escherichia coli; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008080:Liposarcoma / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D055503:Protein Multimerization; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; D051742:Transcription Factor CHOP