RN-TRE IDENTIFIES A FAMILY OF TRE-RELATED PROTEINS DISPLAYING A NOVELPOTENTIAL PROTEIN-BINDING DOMAIN

Eps8 is a recently identified SH3-containing substrate for tyrosine ki nase receptors, To understand the role of eps8 in receptor-mediated si gnaling, we cloned cDNAs encoding proteins that bind to its SH3 domain . One of these cDNAs predicts the synthesis of an 828 amino acid prote in with homology to the N-terminal region of the tre oncogene. We desi gnated this protein RN-tre for Related to the N-terminus of tre. RN-tr e is ubiquitously expressed and maps to 10p13, a region known to be in volved in translocations in various leukemias. Tn addition, a 10p13 mo nosomy syndrome, characterized by developmental alterations, has been reported, The regional homology between RN-tre and tre, which is limit ed to their N-terminal portion, prompted us to investigate the origin of the tre oncogene transcriptional unit. We were able to show that tr e is the fusion product of a 5' genetic element, homologous to RN-tre and a 3' element, encoding a de-ubiquinating enzyme. Moreover, we iden tified, within the N-terminus of RN-tre and tre, a domain (named TrH, for Tre Homology), which is conserved within several proteins from yea st to mammals and has protein-binding properties in vitro.