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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

H  -  Hairless

Drosophila melanogaster

Synonyms: CG5460, Dmel\CG5460, Protein hairless
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Disease relevance of H


High impact information on H

  • Suppressor of Hairless [Su(H)]/Lag-1/RBP-Jkappa/CBF1 is the only known transducing transcription factor for Notch receptor signaling [3].
  • One factor, the Drosophila Suppressor of Hairless protein, is a DNA-binding protein, which suggests that Notch signaling may involve relatively direct signal transmission from the cell surface to the nucleus [4].
  • The signal of N activation may be transduced directly from the cell surface into the nucleus by an evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)], by its regulated nuclear import [5].
  • Loss-of-function mutations of Hairless (H) confer two distinct mutant phenotypes on adult bristles [6].
  • This domain relocates to the nucleus, where it combines with the transcription factor Suppressor of Hairless to regulate gene expression [7].

Biological context of H


Anatomical context of H

  • Gal4 mediated expression of a Notch variant, E(spl) and Hairless shows that the selection of muscle progenitor cells obeys principles apparently identical to those acting at the selection of neural progenitor cells [12].
  • These results indicate that Notch acts in two pathways to determine cell fates in mesoderm: the Delta-to-Notch-to-Suppressor of Hairless-to-Enhancer of split signaling pathway previously defined, and a second pathway that acts independently [13].

Associations of H with chemical compounds

  • The putative Hairless protein deduced from DNA sequencing is extremely basic and highly enriched in serine residues [14].

Physical interactions of H

  • We also find that the Hairless protein interacts with Notch signalling during wing development and inhibits the activity of Su(H) [15].
  • The dCtBP binding motif of Hairless is essential for the function of Hairless in vivo [16].

Enzymatic interactions of H


Regulatory relationships of H

  • We find that Pros26.4 negatively regulates Hairless at the genetic and molecular level [18].
  • The wing phenotype following overexpression of Suppressor of Hairless is strongly enhanced by simultaneous Bx42 RNAi induction in the same tissue [19].

Other interactions of H

  • The DNA-binding transcription factor Suppressor of Hairless [Su(H)] functions as an activator during Notch (N) pathway signaling, but can act as a repressor in the absence of signaling [20].
  • Here we have investigated the requirement for Gro and CtBP in Hairless-mediated repression [9].
  • Finally, we define crucial roles for the adaptor protein Hairless and the co-repressors Groucho and CtBP in conferring repressive activity on Su(H) in the SOP [21].
  • Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal activation of Notch signaling [22].
  • We have isolated the orthologous gene Pros26.4 from Drosophila melanogaster as a molecular interaction partner of Hairless [18].

Analytical, diagnostic and therapeutic context of H


  1. Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J kappa, the homologue of Drosophila Suppressor of Hairless. Zimber-Strobl, U., Strobl, L.J., Meitinger, C., Hinrichs, R., Sakai, T., Furukawa, T., Honjo, T., Bornkamm, G.W. EMBO J. (1994) [Pubmed]
  2. Genetic complexity underlying hybrid male sterility in Drosophila. Sawamura, K., Roote, J., Wu, C.I., Yamamoto, M.T. Genetics (2004) [Pubmed]
  3. A notch-independent activity of suppressor of hairless is required for normal mechanoreceptor physiology. Barolo, S., Walker, R.G., Polyanovsky, A.D., Freschi, G., Keil, T., Posakony, J.W. Cell (2000) [Pubmed]
  4. Notch signaling. Artavanis-Tsakonas, S., Matsuno, K., Fortini, M.E. Science (1995) [Pubmed]
  5. The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling. Lecourtois, M., Schweisguth, F. Genes Dev. (1995) [Pubmed]
  6. The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensory organ development. Bang, A.G., Posakony, J.W. Genes Dev. (1992) [Pubmed]
  7. New alleles of Notch draw a blueprint for multifunctionality. Arias, A.M. Trends Genet. (2002) [Pubmed]
  8. Two isoforms of the Notch antagonist Hairless are produced by differential translation initiation. Maier, D., Nagel, A.C., Preiss, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors. Nagel, A.C., Krejci, A., Tenin, G., Bravo-Patiño, A., Bray, S., Maier, D., Preiss, A. Mol. Cell. Biol. (2005) [Pubmed]
  10. The Drosophila IgC2 domain protein Friend-of-Echinoid, a paralogue of Echinoid, limits the number of sensory organ precursors in the wing disc and interacts with the Notch signaling pathway. Chandra, S., Ahmed, A., Vaessin, H. Dev. Biol. (2003) [Pubmed]
  11. Genetic screen for modifiers of the rough eye phenotype resulting from overexpression of the Notch antagonist hairless in Drosophila. Schreiber, S.L., Preiss, A., Nagel, A.C., Wech, I., Maier, D. Genesis (2002) [Pubmed]
  12. The notch signaling pathway is required to specify muscle progenitor cells in Drosophila. Giebel, B. Mech. Dev. (1999) [Pubmed]
  13. Evidence for a novel Notch pathway required for muscle precursor selection in Drosophila. Rusconi, J.C., Corbin, V. Mech. Dev. (1998) [Pubmed]
  14. Hairless, a Drosophila gene involved in neural development, encodes a novel, serine rich protein. Maier, D., Stumm, G., Kuhn, K., Preiss, A. Mech. Dev. (1992) [Pubmed]
  15. Two different activities of Suppressor of Hairless during wing development in Drosophila. Klein, T., Seugnet, L., Haenlin, M., Martinez Arias, A. Development (2000) [Pubmed]
  16. Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila. Morel, V., Lecourtois, M., Massiani, O., Maier, D., Preiss, A., Schweisguth, F. Curr. Biol. (2001) [Pubmed]
  17. Functional relationships between Notch, Su(H) and the bHLH genes of the E(spl) complex: the E(spl) genes mediate only a subset of Notch activities during imaginal development. de Celis, J.F., de Celis, J., Ligoxygakis, P., Preiss, A., Delidakis, C., Bray, S. Development (1996) [Pubmed]
  18. A molecular link A molecular link between Hairless and Pros26.4, a member of the AAA-ATPase subunits of the proteasome 19S regulatory particle in Drosophila. Müller, D., Nagel, A.C., Maier, D., Preiss, A. J. Cell. Sci. (2006) [Pubmed]
  19. Inducible RNA interference uncovers the Drosophila protein Bx42 as an essential nuclear cofactor involved in Notch signal transduction. Negeri, D., Eggert, H., Gienapp, R., Saumweber, H. Mech. Dev. (2002) [Pubmed]
  20. Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless. Barolo, S., Stone, T., Bang, A.G., Posakony, J.W. Genes Dev. (2002) [Pubmed]
  21. Lateral inhibition in proneural clusters: cis-regulatory logic and default repression by Suppressor of Hairless. Castro, B., Barolo, S., Bailey, A.M., Posakony, J.W. Development (2005) [Pubmed]
  22. Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal activation of Notch signaling. Hori, K., Fostier, M., Ito, M., Fuwa, T.J., Go, M.J., Okano, H., Baron, M., Matsuno, K. Development (2004) [Pubmed]
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