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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    ABSTRACT: RUNX family proteins are expressed from alternate promoters, giving rise to different N-terminal forms, but the functional difference of these isoforms is not understood. Here, we show that growth of a human B lymphoblastoid cell line infected with Epstein-Barr virus is inhibited by RUNX1c but not by RUNX1b. This gives a novel functional assay for the unique N-terminus of RUNX1c, and amino acids of RUNX1c required for the effect have been identified. Primary resting B cells contain RUNX1c, consistent with the growth inhibitory effect in B cells. The oncogene TEL-RUNX1 lacks the N-terminus of RUNX1c because of the TEL fusion and does not inhibit B cell growth. Mouse Runx1c lacks some of the sequences required for human RUNX1c to inhibit B cell growth, indicating that this aspect of human B cell growth control may differ in mice. Remarkably, a cell-penetrating peptide containing the N-terminal sequence of RUNX1c specifically antagonizes the growth inhibitory effect in B lymphoblastoid cells and might be used to modulate the function of human RUNX1c.
    Nucleic Acids Research 12/2012; 41(3). DOI:10.1093/nar/gks1273 · 9.11 Impact Factor
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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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    ABSTRACT: Small ubiquitin-related modifier (SUMO), an ~90 amino acid ubiquitin-like protein, is highly conserved throughout the eukaryotic domain. Like ubiquitin, SUMO is covalently attached to lysine side chains in a large number of target proteins. In contrast to ubiquitin, SUMO does not have a direct role in targeting proteins for proteasomal degradation. However, like ubiquitin, SUMO does modulate protein function in a variety of other ways. This includes effects on protein conformation, subcellular localization, and protein-protein interactions. Significant insight into the in vivo role of SUMOylation has been provided by studies in Drosophila that combine genetic manipulation, proteomic, and biochemical analysis. Such studies have revealed that the SUMO conjugation pathway regulates a wide variety of critical cellular and developmental processes, including chromatin/chromosome function, eggshell patterning, embryonic pattern formation, metamorphosis, larval and pupal development, neurogenesis, development of the innate immune system, and apoptosis. This review discusses our current understanding of the diverse roles for SUMO in Drosophila development.
    12/2012; 2(3):331-49. DOI:10.3390/biom2030331
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