Human homologs of a Drosophila Enhancer of Split gene product define a novel family of nuclear proteins

Abstract

Notch and the m9/10 gene (groucho) of the Enhancer of split (E(spI)) complex are members of the "Notch group" of genes, which is required for a variety of cell fate choices in Drosophila. We have characterized human cDNA clones encoding a family of proteins, designated TLE, that are homologous to the E(spI) m9/10 gene product, as well as a novel Notch-related protein. The TLE genes are differentially expressed and encode nuclear proteins, consistent with the presence of sequence motifs associated with nuclear functions. The structural redundancy implied by the existence of more than one TLE and Notch-homologous gene may be a feature of the human counterparts of the developmentally important Drosophila Notch group genes.

RUNX3 is multifunctional in carcinogenesis of multiple solid tumors

“…Interestingly, RIZ1, also known as PRDM2, is a member of the nuclear histone/protein methyltransferase superfamily that methylates histone 3 Lys 9 (H3K9) residues, whereas CHD5 belongs to the SWI/SNF chromatin modifier family. As with all RUNX family members, RUNX3 encodes a highly conserved C-terminus motif VWRPY that was shown to bind co-repressor proteins TLE1 and Sin3A, which in turn recruit histone deacetylase (Stifani et al, 1992;Aronson et al, 1997;Imai et al, 1998;Levanon et al, 1998).…”

Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates

“…This domain also contains potential phosphorylation sites for cdc2 and casein kinase II in close proximity to a nuclear localization sequence ( Fig. 2A; Stifani et al 1992). The amino terminus has been shown to repress both activated and basal transcription when bound directly to DNA and to have repressor activity equivalent to the full-length protein in several assays, suggesting that this domain is the major intrinsic repression domain (Fisher et al 1996).…”

“…Proteins resembling the Groucho proteins, either consisting of part of the amino terminus but lacking the variable region and WD40 repeats, or consisting of part of the variable region and the WD40 repeats, but lacking the amino terminus, have also been isolated ( Fig. 2C; Stifani et al 1992;Miyasaka et al 1993;Schmidt and Sladek 1993;Choudhury et al 1997). At this time we will not classify these as…”

“…2A,B) (Hartley et al 1988;Stifani et al 1992;Miyasaka et al 1993;Schmidt and Sladek 1993;Choudhury et al 1997;Pflugrad et al 1997;Sharief et al 1997). Proteins resembling the Groucho proteins, either consisting of part of the amino terminus but lacking the variable region and WD40 repeats, or consisting of part of the variable region and the WD40 repeats, but lacking the amino terminus, have also been isolated ( Fig.…”

“…The Groucho proteins serve as non-DNA binding corepressors for specific subsets of DNA-binding transcription factors, including the Hairy-related proteins, Runt domain proteins, Engrailed, and Dorsal, and they are essential for certain aspects of repression by each of these repressors (Paroush et al 1994;Fisher et al 1996;Aronson et al 1997;Dubnicoff et al 1997;Jimenez et al 1997). These family members have been shown to be widely expressed both during development and in the adult, in contrast to the more limited expression pattern of their DNA-binding partners (Hartley et al 1988;Stifani et al 1992;Miyasaka et al 1993;Schmidt and Sladek 1993;Choudhury et al 1997;Pflugrad et al 1997;Sharief et al 1997). In addition, both Groucho and the human family member TLE1 have been shown to actively repress transcription when fused to a heterologous DNA-binding domain and directly bound to DNA (Fisher et al 1996).…”