| Cleavage of Notch1 by Granzyme B Disables Its Transcriptional Activity. | |
| | |
MedLine Citation:
|
PMID: 21548883 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Granzyme-mediated cell death is the main pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. A major player in this process is granzyme B (GrB), which triggers apoptosis in both caspase-dependent and caspase-independent manners. A caspase-independent substrate of GrB is the highly conserved transmembrane receptor Notch1. The GrB cleavage sites in Notch1 and functional consequences of Notch1 cleavage by GrB were unknown. We confirmed that Notch1 is a direct and caspase-independent substrate of GrB. We demonstrate that GrB cleaved the intracellular Notch1 domain at least at two distinct aspartic acids D1860 and D1961. Granzyme B cleavage of Notch1 can occur in all subcellular compartments, during maturation of the receptor, at the membrane, and in the nucleus. GrB also displayed perforin-independent functions by cleaving the extracellular domain of Notch1. Overall, cleavage of Notch1 by GrB resulted in a loss of transcriptional activity, independent of Notch1 activation. We conclude that GrB disables Notch1 function, likely resulting in anti-cellular proliferation and cell death signals. |
| | |
Authors:
|
Geert van Tetering; Niels Bovenschen; Jan Meeldijk; Paul J van Diest; Marc Vooijs |
Related Documents
:
|
21175263 - Ubiquitin ligase c-cbl is involved in tamoxifen-induced apoptosis of mcf-7 cells by dow... 21273783 - Heme oxygenase-1 does not mediate the effects of extracellular acidosis on vascular smo... 11751883 - Nuclear factor-kappa b directs carcinoembryonic antigen-related cellular adhesion molec... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-5-6 |
Journal Detail:
|
Title: The Biochemical journal Volume: - ISSN: 1470-8728 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-5-9 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2984726R Medline TA: Biochem J Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH...
Next Document: Use of a negative selectable marker for rapid selection of recombinant vaccinia virus.