ETO-2, a new member of the ETO-family of nuclear proteins

The t(8;21) is associated with 12-15% of acute myelogenous leukemias of the M2 subtype, the translocation results in the fusion of two genes, AML1 (CB FA2) on chromosome 21 and ETO (MTG8) on chromosome 8, AML1 encodes a DNA bi nding factor; the ETO protein product is less well characterized, but is th ought to be a transcription factor. Here we describe the isolation and char acterization of ETO-2, a murine cDNA that encodes a new member of the ETO f amily of proteins. ETO-2 is 75% identical to murine ETO and shares very hig h sequence identities over four regions of the protein with ETO (domain I-I II and zinc-finger). Northern analysis identifies ETO-2 transcripts in many of the murine tissues analysed and in the developing mouse embryo. ETO-2 i s also expressed in myeloid and erythroid cell lines. We confirmed the nucl ear localization of ETO-2 and demonstrated that domain III and the zinc-fin ger region are not required for nuclear localization. We further showed tha t a region within ETO, containing domain II, mediates dimerization among fa mily members. This region is conserved in the oncoprotein AML-1/ETO. The re cent identification of another ETO-like protein, myeloid translocation gene -related protein 1, together with the data presented here, demonstrates tha t at least three ETO proteins exist with the potential to form dimers in th e cell nucleus.