Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain.
Kopan R, Schroeter EH, Weintraub H, Nye JS.
???displayArticle.abstract???
Previous studies imply that the intracellular domain of Notch1 must translocate to the nucleus for its activity. In this study, we demonstrate that a mNotch1 mutant protein that lacks its extracellular domain but retains its membrane-spanning region becomes proteolytically processed on its intracellular surface and, as a result, the activated intracellular domain (mNotchIC) is released and can move to the nucleus. Proteolytic cleavage at an intracellular site is blocked by protease inhibitors. Intracellular cleavage is not seen in cells transfected with an inactive variant, which includes the extracellular lin-Notch-glp repeats. Collectively, the studies presented here support the model that mNotch1 is proteolytically processed and the cleavage product is translocated to the nucleus for mNotch1 signal transduction.
Artavanis-Tsakonas,
Notch signaling.
1995,
Pubmed Aster,
Functional analysis of the TAN-1 gene, a human homolog of Drosophila notch.
1994,
Pubmed Brou,
Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless.
1994,
Pubmed Coffman,
Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos.
1993,
Pubmed
,
Xenbase Crittenden,
GLP-1 is localized to the mitotic region of the C. elegans germ line.
1994,
Pubmed Del Amo,
Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development.
1992,
Pubmed
,
Xenbase Evan,
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
1985,
Pubmed
,
Xenbase Fehon,
Complex cellular and subcellular regulation of notch expression during embryonic and imaginal development of Drosophila: implications for notch function.
1991,
Pubmed Fortini,
The suppressor of hairless protein participates in notch receptor signaling.
1994,
Pubmed Fortini,
An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye.
1993,
Pubmed Jarriault,
Signalling downstream of activated mammalian Notch.
1995,
Pubmed Jennings,
The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo.
1994,
Pubmed Kidd,
Structure and distribution of the Notch protein in developing Drosophila.
1989,
Pubmed Kopan,
The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD.
1994,
Pubmed LaMarco,
Identification of Ets- and notch-related subunits in GA binding protein.
1991,
Pubmed Lieber,
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,
Pubmed Matsuno,
Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats.
1995,
Pubmed Nye,
Developmental signaling. Vertebrate ligands for Notch.
1995,
Pubmed Nye,
An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells.
1994,
Pubmed Pati,
Novel vectors for expression of cDNA encoding epitope-tagged proteins in mammalian cells.
1992,
Pubmed Rebay,
Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor.
1993,
Pubmed Rechsteiner,
Regulation of enzyme levels by proteolysis: the role of pest regions.
1988,
Pubmed Roehl,
Control of cell fate in C. elegans by a GLP-1 peptide consisting primarily of ankyrin repeats.
1993,
Pubmed Sasai,
Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split.
1992,
Pubmed Schweisguth,
Antagonistic activities of Suppressor of Hairless and Hairless control alternative cell fates in the Drosophila adult epidermis.
1994,
Pubmed Schweisguth,
Suppressor of Hairless is required for signal reception during lateral inhibition in the Drosophila pupal notum.
1995,
Pubmed Struhl,
Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo.
1993,
Pubmed Thompson,
Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex.
1991,
Pubmed Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase Wang,
SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.
1994,
Pubmed Watanabe,
cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs.
1993,
Pubmed Zagouras,
Alterations in Notch signaling in neoplastic lesions of the human cervix.
1995,
Pubmed
