Crozat A, Aman P, Mandahl N, Ron D
Department of Medicine, NYU Medical Center, New York 10016.
Nature. 1993 Jun 17;363(6430):640-4. doi: 10.1038/363640a0.
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.
人类黏液样脂肪肉瘤含有一种特征性的染色体易位，即t(12;16)(q13;p11)，它与编码CHOP的基因的结构重排相关，CHOP是一种生长停滞和DNA损伤诱导因子，属于位于12q13.1的C/EBP转录因子家族成员。我们在此使用CHOP特异性互补探针和抗血清报告这些肿瘤中存在异常的CHOP转录本和蛋白质。对易位相关的CHOP基因产物进行克隆，发现CHOP与一个暂命名为TLS（在脂肪肉瘤中易位）的基因发生了融合。TLS是一种新型的核RNA结合蛋白，与EWS具有广泛的序列相似性，EWS是一种在尤因肉瘤中常见的易位基因的产物。在TLS-CHOP中，TLS的RNA结合结构域被CHOP的DNA结合和亮氨酸拉链二聚化结构域所取代。将RNA结合蛋白的保守效应结构域靶向DNA可能在肿瘤形成中起作用。
