The suppressor of hairless protein participates in notch receptor signaling

In a genetic screen for mutations that attenuate Notch signaling in the developing Drosophila eye, we isolated rare, gain-of-function alleles of Suppressor of Hairless (Su(H)), the fly homolog of the mammalian C promoter-binding factor 1 (CBF1) gene. Su(H) exhibits numerous allele-specific genetic interactions with Notch as well as with Delta, deltex, and mastermind. In cultured Drosophila cells, the Su(H) protein is sequestered in the cytoplasm when coexpressed with Notch protein and is translocated to the nucleus when Notch binds to its ligand Delta. Cytoplasmic retention of Su(H) requires the intracellular cdc10/ankyrin repeats of Notch, which associate with Su(H) protein in the yeast interaction trap assay. These results indicate that Notch activity may regulate nuclear events by controlling the activity of a DNA-binding protein.

[1]  G. Struhl,et al.  Intrinsic activity of the lin-12 and Notch intracellular domains in vivo , 1993, Cell.

[2]  T. Honjo,et al.  The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development , 1992, Cell.

[3]  T. Honjo,et al.  Recognition sequence of a highly conserved DNA binding protein RBP-Jx , 1994 .

[4]  D. Smoller,et al.  The Drosophila neurogenic locus mastermind encodes a nuclear protein unusually rich in amino acid homopolymers. , 1990, Genes & development.

[5]  T. Honjo,et al.  The recombination signal sequence-binding protein RBP-2N functions as a transcriptional repressor , 1994, Molecular and cellular biology.

[6]  U. Dietrich,et al.  Functional interactions of neurogenic genes of Drosophila melanogaster. , 1988, Genetics.

[7]  P. Simpson,et al.  The choice of cell fate in the epidermis of Drosophila , 1991, Cell.

[8]  D. Nash.  THE EXPRESSION OF "HAIRLESS" IN DROSOPHILA AND THE ROLE OF TWO CLOSELY LINKED MODIFIERS OF OPPOSITE EFFECT. , 1965, Genetical research.

[9]  R. Fehon,et al.  Implications of dynamic patterns of Delta and Notch expression for cellular interactions during Drosophila development. , 1993, Development.

[10]  C. Plunkett.  The interaction of genetic and environmental factors in development , 1926 .

[11]  P. Portin.  Allelic negative complementation at the Abruptex locus of Drosophila melanogaster. , 1975, Genetics.

[12]  H. Roehl,et al.  Control of cell fate in C. elegans by a GLP-1 peptide consisting primarily of ankyrin repeats , 1993, Nature.

[13]  M. W. Young,et al.  Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors , 1986, Molecular and cellular biology.

[14]  Stefano Stifani,et al.  Human homologs of a Drosophila Enhancer of Split gene product define a novel family of nuclear proteins , 1992, Nature Genetics.

[15]  S. Artavanis-Tsakonas,et al.  Complex cellular and subcellular regulation of notch expression during embryonic and imaginal development of Drosophila: implications for notch function , 1991, The Journal of cell biology.

[16]  Tian Xu,et al.  Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila , 1990, Cell.

[17]  R. Brent,et al.  Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites , 1993, Cell.

[18]  T. Honjo,et al.  A protein binding to the Jk recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif , 1989, Nature.

[19]  M. Ashburner.  The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. III. Hypomorphic and hypermorphic mutations affecting the expression of hairless. , 1982, Genetics.

[20]  G K Lewis,et al.  Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product , 1985, Molecular and cellular biology.

[21]  D. Lindsley,et al.  The Genome of Drosophila Melanogaster , 1992 .

[22]  T. Honjo,et al.  The Drosophila RBP-J kappa gene encodes the binding protein for the immunoglobulin J kappa recombination signal sequence. , 1991, The Journal of biological chemistry.

[23]  S. Artavanis-Tsakonas,et al.  A member of the Notch group of interacting loci, deltex encodes a cytoplasmic basic protein. , 1994, Genetics.

[24]  Gerald M. Rubin,et al.  Making a difference: The role of cell-cell interactions in establishing separate identities for equivalent cells , 1992, Cell.

[25]  G. G. Foster.  Negative complementation at the notch locus of Drosophila melanogaster. , 1975, Genetics.

[26]  R. J. Fleming,et al.  The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis. , 1990, Genes & development.

[27]  G. Rubin,et al.  Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase , 1991, Cell.

[28]  D. Nash.  The Mutational Basis for the "Allelic" Modifier Mutants, ENHANCER and SUPPRESSOR OF HAIRLESS, of DROSOPHILA MELANOGASTER. , 1970, Genetics.

[29]  S. Artavanis-Tsakonas,et al.  Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor , 1993, Cell.

[30]  M. W. Young,et al.  Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei. , 1993, Genes & development.

[31]  J. Posakony,et al.  Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal-binding protein gene, controls sensory organ cell fates , 1992, Cell.

[32]  S. Artavanis-Tsakonas,et al.  Cytosolic interaction between deltex and Notch ankyrin repeats implicates deltex in the Notch signaling pathway. , 1994, Development.

[33]  S. Artavanis-Tsakonas,et al.  Choosing a cell fate: a view from the Notch locus. , 1991, Trends in genetics : TIG.

[34]  V. Hartenstein,et al.  The function of the neurogenic genes during epithelial development in the Drosophila embryo. , 1992, Development.

[35]  M. Muskavitch,et al.  The pleiotropic function of Delta during postembryonic development of Drosophila melanogaster. , 1993, Genetics.

[36]  M. Fortini,et al.  An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye , 1993, Nature.

[37]  R. Cagan,et al.  Notch is required for successive cell decisions in the developing Drosophila retina. , 1989, Genes & development.

[38]  M. Fortini,et al.  Notch: Neurogenesis is only part of the picture , 1993, Cell.

[39]  R. J. Fleming,et al.  Specific EGF repeats of Notch mediate interactions with Delta and serrate: Implications for notch as a multifunctional receptor , 1991, Cell.

[40]  J. Mohler,et al.  Temperature-sensitive mutations of the notch locus in Drosophila melanogaster. , 1975, Genetics.

[41]  S. Artavanis-Tsakonas,et al.  Two genetically and molecularly distinct functions involved in early neurogenesis reside within the Enhancer of split locus of Drosophila melanogaster. , 1991, Genetics.

[42]  P. Ling,et al.  Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa. , 1994, Science.

[43]  S. Artavanis-Tsakonas,et al.  Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeats , 1985, Cell.

[44]  A. Bang,et al.  The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development. , 1992, Genes & development.

[45]  D. Maier,et al.  Hairless, a Drosophila gene involved in neural development, encodes a novel, serine rich protein , 1992, Mechanisms of Development.