The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas.
Children exposed to radioactive iodine as a consequence of the Chernobyl reactor accident have an increased risk of papillary thyroid carcinomas (PTC). The predominant molecular lesions in these tumors are rearrangements of the RET receptor tyrosine kinase (tk). Here we report on two novel types of RET rearrangement, PTC6 and 7, and describe the fusion products and the ret fused gene (rfg) proteins. Like the other rfg proteins identified so far they are ubiquitously expressed, not membrane-bound and contain coiled coil domains required for constitutive activation of the ret tk domain. In the PTC6 rearrangement the ret tk domain is fused to the aminoterminal part of the human transcription intermediary factor htif 1. In the PTC7 rearrangement the ret tk domain is fused to a novel protein that is strongly related to htif1. Like htif1 it contains a RBCC motif (ring finger, B boxes, coiled coil domain) located in the aminoterminal part and a phd finger and a bromodomain in the carboxyterminal part. Htif1 and related proteins are transcription coactivators for nuclear receptors, thus participating in controlling cellular development, differentiation and homeostasis. This is the first report on their involvement in human thyroid carcinogenesis.
Klugbauer
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Institute of Pathology, Ludwig Maximilians University of Munich, Germany.
Rabes
H M
HM
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism*; D002675:Child, Preschool; D029721:Drosophila Proteins; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D011210:Power Plants; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D012313:RNA / Q000032:analysis; D018788:Radioactive Hazard Release; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics; D002094:Republic of Belarus; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D014455:Ukraine
D029721:Drosophila Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1; D012313:RNA; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila