The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator.

摘要: Molecular characterization of malignant melanoma soft parts or tissue clear cell sarcoma which shares t(12;22) chromosome translocation revealed fusion EWS with a transcriptional factor gene ATF-1. The gene, encodes an RNA binding protein, was also shown to be involved in Ewing sarcoma, related primitive neuroectodermal tumors and desmoplastic small round tumors. In order understand the functional role EWS-ATF-1 chimeric protein human solid tumors, we have cloned aberrant ATF-1 (EWS-ATF-1) cDNA studied its DNA binding, activation properties compared normal protein. Our results demonstrate that binds weakly vitro but functions as efficient constitutive activator unlike needs induced cAMP. Deletion analysis EWS-fusion domain regulatory for leucine zipper loss suggesting protein-protein interaction play EWS-ATF-1. We negatively regulates activity Therefore replacement part amino-terminal kinase altered interactions causing deregulated expression may responsible genesis translocation-bearing Targeting cofactors (CBP, etc) by proteins could one mechanisms neoplasia.