Notch signal transduction: A real Rip and more

Current Opinion in Genetics and Development

Volumn 10, Issue 4, 2000, Pages 363-369

  Weinmaster, Gerry ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NOTCH RECEPTOR;

MORPHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW; SIGNAL TRANSDUCTION;

EID: 0033920919     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(00)00097-6     Document Type: Review

References (65)

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16. Struhl G., Greenwald I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature. 398:1999;522-525. Null alleles of Drosophila presenilin were isolated and shown to have identical neurogenic phenotypes as found with losses in Notch activity. Gal4-VP16 chimeric Notch constructs expressed in PS mutant embryos were tested for UAS-lacZ expression as a measure of proteolytic release and translocation of the Notch intracellular domain to the nucleus. Both ligand-independent membrane-bound Notch and full-length Notch required PS to function whereas a soluble intracellular form of Notch activated lacZ expression in the absence of PS consistent with a role for PS in proteolytic release of the Notch intracellular domain.
17. Ye Y., Lukinova N., Fortini M.E. Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants. Nature. 398:1999;525-529. Western-blot analysis of Drosophila larval extracts detects aberrant processing of Notch in mutants indicating that PS is required for some aspect of Notch processing. The increase in higher molecular weight cleavage fragments of Notch in the absence of PS may reflect the accumulation of an extracellular cleavage product in the absence of PS activity. The Notch subcellular distribution in PS mutants appears normal suggesting that protein trafficking is not affected by loss in PS activity. In contrast to other reports, a ligand-independent membrane-bound form of Notch lacking most of the extracellular domain functions in the absence of PS. Moreover, a Notch mutant that retains the extracellular sequences thought to negatively regulate Notch is also active and its activity does not require PS. The reason for these differences is not clear.
18. Wong P.C., Zheng H., Chen H., Becher M.W., Sirinathsinghji D.J., Trumbauer M.E., Chen H.Y., Price D.L., Van der Ploeg L.H., Sisodia S.S. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature. 387:1997;288-292.
19. Swiatek P.J., Lindsell C.E., del Amo F.F., Weinmaster G., Gridley T. Notch1 is essential for postimplantation development in mice. Genes Dev. 8:1994;707-719.
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21. ΔE, suggesting that a presenilin-dependent γ-secretase may function in the proteolytic release of the Notch intracellular domain.
22. Song W., Nadeau P., Yuan M., Yang X., Shen J., Yankner B.A. Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations. Proc Natl Acad Sci USA. 96:1999;6959-6963. NICD generation from membrane-bound forms of Notch is decreased in cells deficient in PS1 and this processing defect is rescued by the expression of PS1. Interestingly, PS1 mutant proteins associated with Alzheimer's disease are impaired in their ability to rescue the defect in NICD production detected in PS1-deficient cells. Ligand-independent membrane bound forms of Notch1 are processed to different levels depending on either the presence or absence of sequences downstream of the ankyrin repeats, suggesting that these sequences may be involved either in the generation or turnover of NICD.
23. ΔE where it could function in proteolytic release of NICD. Biotin-labeled unprocessed Notch and heterodimeric Notch coimmunoprecipitate with PS1, indicating that both forms of Notch are complexed with PS1 at the cell surface.
24. Davis J.A., Naruse S., Chen H., Eckman C., Younkin S., Price D.L., Borchelt D.R., Sisodia S.S., Wong P.C. An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos. Neuron. 20:1998;603-609.
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26. Berezovska O., Jack C., McLean P., Aster J.C., Hicks C., Xia W., Wolfe M.S., Taylor Kimberly W., Weinmaster G., Selkoe D., Hyman B.T. Two transmembrane aspartate mutationin presenilin impair Notch1 proteolysis and nuclear translocation with relative preservation of Notch signaling. J Neurochem. 2000;. in press.
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29. Brou C., Logeat F., Gupta N., Bessia C., LeBail O., Doedens J.R., Cumano A., Roux P., Black R.A., Israel A. A novel proteolytic cleavage involved in Notch signaling: the role of the Disintegrin-Metalloprotease TACE. Mol Cell. 5:2000;207-216. A cleavage site in the extracellular domain of Notch is identified and the protease activity that cleaves this site is purified and found to have characteristics of a metalloproteinase of the ADAM family, TACE. TACE is shown to cleave a chimeric Notch at the identified site in vitro and mutations at this site prevent the cleavage. As Kuz does not copurify with this activity it is concluded that Kuz does not cleave the Notch extracellular domain.
30. •] using a different chimeric Notch protein, and mutation at this site prevents cleavage. Metalloproteinase inhibitors prevent cleavage at the identified site, suggesting that a metalloproteinase is involved; however, because cleavage in the Notch extracellular domain takes place in Kuz-deficient cells, it does not appear that this metalloproteinase is directly involved in the cleavage. Cleavage at a previously identified site within the Notch transmembrane domain involved in the release of the NICD is prevented through mutation of the extracellular site, suggesting that cleavage in the extracellular domain facilitates the intramembrane cleavage and release of NICD from the membrane. A proteolytic cascade is proposed to regulate Notch signaling.
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33. Logeat F., Bessia C., Brou C., LeBail O., Jarriault S., Seiday N., Israel A. The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci USA. 95:1998;8108-8112.
34. Rand M.D., Grimm L.M., Artavanis-Tsakonas S., Patriub V., Blacklow S.C., Sklar J., Aster J.C. Calcium depletion dissociates and activates heterodimeric notch receptors. Mol Cell Biol. 20:2000;1825-1835. The authors of this paper demonstrate that association between the Notch1 furin cleavage fragments is stabilized through noncovalent interactions that are calcium dependent. Interestingly, dissociation of the amino-terminal and carboxy-terminal cleavage fragments is correlated with generation of a smaller carboxy-terminal cleavage fragment, a signal for Notch in the nucleus and activation of CBF1-dependent transcription. A model for ligand induced activation of Notch signaling through dissociation of heterodimeric Notch is presented.
35. Jarriault S., Le Bail O., Hirsinger E., Pourquié O., Logeat F., Strong C.F., Brou C., Seidah N.G., Isra l.A. Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Mol Cell Biol. 18:1998;7423-7431.
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40. Pan D., Rubin G.M. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell. 90:1997;271-280.
41. Wen C., Metzstein M.M., Greenwald I. SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling. Development. 124:1997;4759-4767.
42. Sotillos S., Roch F., Campuzano S. The metalloprotease-disintegrin Kuzbanian participates in Notch activation during growth and patterning of Drosophila imaginal discs. Development. 124:1997;4769-4779.
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44. Weinmaster G. The ins and outs of notch signaling. Mol Cell Neurosci. 9:1997;91-102.
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46. Klueg K.M., Parody T.R., Muskavitch M.A. Complex proteolytic processing acts on Delta, a transmembrane ligand for Notch, during Drosophila development. Mol Biol Cell. 9:1998;1709-1723.
47. Han W., Ye Q., Moore M.A. A soluble form of human delta-like-1 inhibits differentiation of hematopoietic progenitor cells. Blood. 95:2000;1616-1625.
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49. Brown M.S., Ye J., Rawson R.B., Goldstein J.L.Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans Cell. 100:2000;391-398. An excellent review covering a recently described exciting new mechanism of gene regulation termed Rip in which sequential proteolysis functions to release fragments of receptors from the membrane to allow their transit to the nucleus to regulate gene expression. A number of examples are clearly and concisely described.
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51. Parks A.L., Klueg K.M., Stout J.R., Muskavitch M.A. Ligand endocytosis drives receptor dissociation and activation in the Notch pathway. Development. 127:2000;1373-1385. An interesting study in which immunostaining for Notch in the developing Drosophila retina reveals that the Notch extracellular domain and its intracellular domain reside in different cellular compartments but when endocytosis is blocked they are colocalized. A model in which ligand-induced endocytosis is the driving force behind proteolytic release of the Notch intracellular domain and downstream signaling is presented.
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57. intra, a signal for Notch was not detected in the nucleus.
58. Cornell M., Evans D.A., Mann R., Fostier M., Flasza M., Monthatong M., Artavanis-Tsakonas S., Baron M. The Drosophila melanogaster Suppressor of deltex gene, a regulator of the Notch receptor signaling pathway, is an E3 class ubiquitin ligase. Genetics. 152:1999;567-576.
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60. Sestan N., Artavanis-Tsakonas S., Rakic P. Contact-dependent inhibition of cortical neurite growth mediated by notch signaling. Science. 286:1999;741-746. Evidence is here presented that Notch signaling in cortical neurons regulates extension and elaboration of neurites. Neurites of neurons cultured at a high density were short and highly branched and this phenotype correlates with a strong signal for Notch in the nucleus, activation of CSL-reporters and induction of HES genes, suggesting that contact-dependent inhibition of neurite growth is regulated by Notch signaling. Constitutively active Notch also inhibits neurite growth whereas inhibition of Notch signaling promotes neurite extension.
61. Ligoxygakis P., Yu S.Y., Delidakis C., Baker N.E. A subset of notch functions during Drosophila eye development require Su(H) and the E(spl) gene complex. Development. 125:1998;2893-2900.
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65. Nofziger D., Miyamoto A., Lyons K.M., Weinmaster G. Notch signaling imposes two distinct blocks in the differentiation of C2C12 myoblasts. Development. 126:1999;1689-1702.