Rhombotin-2 (RBTN-2) is a proto-oncogene only in the context transcription factors. For example, RBTN-2 has recently been of T lymphocytes. We postulated that the oncogenic effect of shown to bind erythroid transcription factors tal-1, GATA-1,
RBTN-2 in T cells is likely mediated by binding protein(s) withand GATA-2. 9 These data, considered in light of the nuclear T cell-specific expression. By screening a T cell cDNA library, location of RBTN-2 in hematopoietic cells, 7 suggest that we identified a novel ets transcription factor that binds RBTN-RBTN-2 has a direct role in transcriptional regulation of 2. This protein was named elf-2 because its DNA-binding domain is virtually identical to that of ets family member elf-1. erythroid development. RBTN-2 may also regulate other Northern analyses showed similar levels of two elf-2 transcripts genes. For example, RBTN-2 likely regulates the expression of RBTN-2 binds other proteins via its two tandem LIM domains, which make up approximately two-thirds of its mass Introduction (reviewed in Ref. 11). Each LIM domain coordinates two zinc cations, which presumably hold the intervening residues in The proto-oncogene rhombotin-2 (RBTN-2) was initially loop-like structures reminiscent of zinc finger domains. The implicated in T cell leukemogenesis by the high frequency of residues required for zinc cation-coordination and structural non-random chromosomal translocations involving the RBTNintegrity are highly conserved. The other amino acid residues, 2 locus (at 11p13) in childhood T cell acute leukemia. 1,2 and to some degree the length of the LIM domain loop porThese translocations almost invariably result in the high tions are variable, and thus confer each LIM domain its own expression of RBTN-2 in T cells where RBTN-2 is not normally specific function. LIM domains have been shown to facilitate expressed. 2,3 Recent transgenic studies have confirmed the a variety of protein-protein interactions. 9,12,13 For example, role of RBTN-2 as a proto-oncogene. Enforced expression of the LIM domains of RBTN-2 mediate its binding to tal-1 13 and RBTN-2 in T cells of transgenic mice results in T cell lym-RBP2 (Mao S, Neale GAM, Bram RJ, Goorha RM, submitted). phoma and leukemia. [4][5][6] The oncogenic effects of RBTN-2 are Thus, RBTN-2's functions are likely mediated by specific pro-T cell specific. Transgenic mice overexpressing RBTN-2 in all tein-protein interactions through its LIM domains. tissues do not show any type of cancer other than T cellAlthough it is clear that the inappropriate expression of leukemia/lymphoma. 6 The inappropriate expression of RBTN-RBTN-2 in T cells results in leukemia, the molecular 2 in thymocytes causes proliferation of immature T cells prior mechanism(s) of this are not yet understood. Because RBTNto overt leukemia/lymphoma. 5,6 2 exerts its normal functions by binding to different proteins, In addition to its involvement in T cell leukemia/lymphoma, it seemed reasonable to evaluate whether RBTN-2's involve-RBTN-2 plays multiple roles in normal c...