[
Curr Biol,
2000]
During signaling by the Notch receptor, Notch's intracellular domain is cleaved, moves to the nucleus and associates with a DNA-binding protein of the CSL class (CSL for CBF1, Suppressor of Hairless (Su(H)), LAG-1); as a result, target genes are transcriptionally activated (reviewed in [1,2]). In Caenorhabditis elegans, a glutamine-rich protein called LAG-3 forms a ternary complex with the Notch intracellular domain and LAG-1 and appears to serve as a transcriptional activator that is critical for signaling [3]. Although database searches failed to identify a LAG-3-related protein, we surmised that Notch signaling in other organisms might involve an analogous activity.
[
Nat Genet,
1992]
Human pre-B cell acute lymphoblastic leukaemias are associated with a chimaeric gene that is generated from a t(1;19) chromosomal translocation. This fusion joins the regulatory regions of the lymphoid transcription factor gene, E2A, to the C-terminal region, including the homeodomain, of PBX1 (previously called prl). Tow additional human genes (PBX2 and PBX3) with 77-84% identity to PBX1 have been isolated based on sequence similarity. These genes, however, are too closely related to distinguish between recent divergence and conserved essential motifs, if any, outside the homeodomain. Such conserved domains might be revealed by comparing mammalian sequences with those of more evolutionarily distant organisms, such as the expressed sequence tags (ESTs) generated recently in Caenorhabditis elegans.