Abstract
Notch, a transmembrane protein found in a wide range of organisms, is a component of a pathway that mediates cell-fate decisions that involve intercellular communication. In this paper, we show that inDrosophila melanogaster, Notch (N) is processed in a ligand-dependent fashion to generate phosphorylated, soluble intracellular derivatives. Suppressor of Hairless [Su(H)] is predominantly associated with soluble intracellular N. It has been demonstrated by others that N has access to the nucleus, and we show that when tethered directly to DNA, the cytoplasmic domain of N can activate transcription. Conversely, a viral activator fused to Su(H) can substitute for at least some N functions during embryogenesis. We suggest that one function of soluble forms of N is to bind to Su(H), and in the nucleus, to act directly as a transcriptional transactivator of the latter protein. Although N has functional nuclear localization signals, the N/Su(H) complex accumulates in the cytoplasm and on membranes suggesting that its nuclear entry is regulated. Localization studies in cultured cells and embryos suggest that Su(H) plays a role in this regulation, with the relative levels of Delta, N and Su(H) determining whether a N/Su(H) complex enters the nucleus.
References
60
Referenced
196
10.1093/nar/19.9.2499
10.1126/science.7716513
10.1101/gad.7.7b.1325
10.1101/gad.9.21.2609
10.1016/S0092-8674(00)80336-0
10.1242/dev.118.2.401
/ Development / Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. by Brand (1993)10.1016/S0092-8674(00)80213-5
10.1016/0022-2836(84)90427-3
10.1093/genetics/144.4.1673
/ Genetics / The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. by Chou (1996)10.1242/dev.119.4.1359
/ Development / Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras. by Chou (1993)10.1093/genetics/136.1.183
/ Genetics / Modifications of the Notch function by Abruptex mutations in Drosophila melanogaster. by de Celis (1994)10.1101/gad.10.4.421
10.1016/S0021-9258(17)44109-3
/ J. Biol. Chem. / LexA protein is a repressor of the colicin E1 gene. by Ebina (1983)10.1126/science.280.5365.895
10.1093/nar/26.1.85
10.1016/0092-8674(94)90196-1
10.1093/genetics/81.1.99
/ Genetics / Negative complementation at the Notch locus of Drosophila melanogaster. by Foster (1975)10.1073/pnas.93.21.11925
10.1242/dev.122.6.1673
/ Development / Subcellular localization of Suppressor of Hairless in Drosophila sense organ cells during Notch signalling. by Gho (1996)10.1101/gad.12.12.1751
10.1016/0092-8674(93)90498-F
10.1016/0092-8674(91)90263-X
10.1016/0092-8674(86)90353-3
10.1038/377355a0
10.1242/dev.120.12.3537
/ Development / The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo. by Jennings (1994)10.1101/gad.12.15.2269
10.1242/dev.124.20.4133
/ Development / Involvement of RBP-J in biological functions of mouse Notch 1 and its derivatives. by Kato (1997)10.1016/0092-8674(87)90123-1
10.1016/0092-8674(92)90596-5
{'key': '2021111418584034000_12.23.3728.30', 'first-page': '3094', 'article-title': 'Sequence of the Notch locus of Drosophila: Relationship of the encoded protein to mammalian clotting and growth factors.', 'volume': '6', 'author': 'Kidd', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Sequence of the Notch locus of Drosophila: Relationship of the encoded protein to mammalian clotting and growth factors. by Kidd (1986)10.1101/gad.3.8.1113
10.1126/science.274.5293.1652
10.1073/pnas.93.4.1683
10.1101/gad.9.21.2598
10.1016/S0960-9822(98)70300-8
10.1101/gad.7.10.1949
10.1073/pnas.95.14.8108
10.1242/dev.121.8.2633
/ Development / Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats. by Matsuno (1995)10.1242/dev.124.21.4265
/ Development / Suppressor of Hairless-independent events in Notch signaling imply novel pathway elements. by Matsuno (1997)10.1016/S0960-9822(95)00189-8
10.1016/S0092-8674(00)80335-9
10.1006/dbio.1993.1151
10.1093/genetics/108.3.559
/ Genetics / Developmental genetics of the 2E-F region the Drosophila X chromosome: A region rich in ‘Developmentally important’ genes. by Perrimon (1984)10.1093/genetics/81.1.121
/ Genetics / Allelic negative complementation at the Abruptex locus of Drosophila melanogaster. by Portin (1975)10.1016/0092-8674(91)90064-6
10.1016/0092-8674(93)90423-N
10.1002/j.1460-2075.1996.tb01092.x
/ EMBO J. / Roles of the RAM and ANK domains in signalling by the C. elegans GLP-1 receptor. by Roehl (1996)10.1126/science.2876518
10.1038/30756
10.1016/0092-8674(92)90641-O
10.1242/dev.120.6.1433
/ Development / Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis. (1994)10.1016/0092-8674(89)90060-3
10.1038/ng1092-119
10.1016/S0092-8674(00)81193-9
10.1016/0092-8674(93)90424-O
10.1016/S0960-9822(95)00279-X
10.1242/dev.124.3.693
/ Development / The Xenopus homolog of Drosophila Suppressor of Hairless mediates Notch signaling during primary neurogenesis. by Wettstein (1997)10.1016/0092-8674(85)90229-6
10.1016/0925-4773(95)00451-3
10.1242/dev.117.4.1223
/ Development / Analysis of genetic mosaics in developing and adult Drosophila tissues. by Xu (1993)
Dates
Type | When |
---|---|
Created | 17 years, 6 months ago (Feb. 20, 2008, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 10:26 p.m.) |
Indexed | 2 months, 2 weeks ago (June 10, 2025, 2:06 p.m.) |
Issued | 26 years, 8 months ago (Dec. 1, 1998) |
Published | 26 years, 8 months ago (Dec. 1, 1998) |
Published Online | 26 years, 8 months ago (Dec. 1, 1998) |
Published Print | 26 years, 8 months ago (Dec. 1, 1998) |
@article{Kidd_1998, title={Ligand-induced cleavage and regulation of nuclear entry of Notch in Drosophila melanogaster embryos}, volume={12}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.12.23.3728}, DOI={10.1101/gad.12.23.3728}, number={23}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Kidd, Simon and Lieber, Toby and Young, Michael W.}, year={1998}, month=dec, pages={3728–3740} }