Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins [published erratum appears in Nat Genet 1992 Dec;2(4):343]

Howard Hughes Medical Institute, Boyer Centre for Molecular Medicine, New Haven, Connecticut.
Nature Genetics (Impact Factor: 29.35). 06/1993; 2(4):343. DOI: 10.1038/ng1292-343a
Source: PubMed


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.

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    • "(termed RAM23 domain (Tamura et al. 1995) and seven CDC10/ankyrin repeats flanked by nuclear localisation signals (Stifani et al., 1992; Fleming 1998; Mumm and Kopan 2000; Fig. 2). The ankyrin motif was previously found in Cdc10 and SWI6 proteins of yeast, and is thought to mediate protein-protein interactions (Breeden and Nasmyth 1987; Bennet 1992). "

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    • "The extreme C-terminus contains the VWRPY sequence, through which TLE family transcriptional repressors are recruited (24,25). The VWRPY deletion mutant (RUNX1cΔVWRPY) repressed the growth of the IB4 cells to a similar extent as RUNX1c (Figure 6C), indicating that it is not required for the growth repressive activity of RUNX1c in this context. "
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    • "Gro contains highly conversed regions at its N and C-termini (the Q and WD-repeat domains, respectively) that are essential for function and a poorly conserved central region (consisting of GP, CcN, and SP domains) [54]. While these central domains appear to be disordered, they nonetheless play critical positive and negative roles in repression–the GP and CcN domains are required for repression, while the SP domain dampens Gro function, and therefore its deletion results in Gro hyperactivity [55]. "
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