ELF-2, A RHOMBOTIN-2 BINDING ETS TRANSCRIPTION FACTOR - DISCOVERY ANDPOTENTIAL ROLE IN T-CELL LEUKEMIA

Rhombotin-2 (RBTN-2) is a proto-oncogene only in the context of T lymp hocytes. We postulated that the oncogenic effect of RBTN-2 in T cells is likely mediated by binding protein(s) with T cell-specific expressi on. By screening a T cell cDNA library, we identified a novel ets tran scription factor that binds RBTN-2. This protein was named elf-2 becau se its DNA-binding domain is virtually identical to that of ets family member elf-1. Northern analyses showed similar levels of two elf-2 tr anscripts (3.5 kb and 3.8 kb) in all tissues except thymus. Thymocytes expressed four- to 10-fold greater amounts of the 3.5 kb transcript t han other tissues. Sequence analyses of cDNA clones indicated that the se transcripts encode proteins differing only at their amino termini, and likely represent alternatively spliced isoforms. These isoforms (e lf-2a and elf-2b) contain identical RBTN-2 binding regions and DNA-bin ding domains. Elf-2b lacks a putative transactivation domain. The expr ession patterns suggest that RBTN-2 normally interacts equally with el f-2a and elf-2b. In contrast, when RBTN-2 is inappropriately expressed in T cells, RBTN-2 would interact predominantly with elf-2b; this int eraction may lead to T cell proliferation.