Disease relevance of H

• 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 [1].
• The 450-kb region between two genes, Suppressor of Hairless and snail, exhibited a strong effect on the sterility [2].

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

• However, although there is no indication for alternative splicing, two Hairless protein isoforms, H(p120) and H(p150), are observed throughout development [8].
• Notch signal transduction centers on a conserved DNA-binding protein called Suppressor of Hairless [Su(H)] in Drosophila species [9].
• In contrast, overexpression of Hairless, a negative regulator of the Notch pathway, and decreased Su(H) activity enhance these phenotypes [10].
• These phenotypes are suppressed by overexpression of Notch, Suppressor of Hairless [Su(H)], and Enhancer of split m7 [10].
• Molecularly, Hairless inhibits Notch target gene activation by directly binding to the Notch signal transducer Su(H) [11].

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

• We suggest that the Notch pathway bifurcates after the activation of Suppressor of Hairless and that Enhancer of split activity is not required when the consequence of Notch function is the transcriptional activation of downstream genes [17].

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

• Here, we report the molecular cloning of the Hairless locus, confirmed by breakpoint and transformation analysis [14].

References