Prospects & Overviews
Notch: Implications of endogenous inhibitors for therapy
Article first published online: 18 MAY 2010
Copyright © 2010 WILEY Periodicals, Inc.
Volume 32, Issue 6, pages 481–487, June 2010
How to Cite
Dikic, I. and Schmidt, M. H. H. (2010), Notch: Implications of endogenous inhibitors for therapy. Bioessays, 32: 481–487. doi: 10.1002/bies.200900140
- Issue published online: 18 MAY 2010
- Article first published online: 18 MAY 2010
- German Research Foundation DFG
- Excellence Cluster 147 ‘Cardio-Pulmonary Systems’
- neural stem cells;
- Notch inhibitor;
- Notch signalling
Soluble components of Notch signalling can be applied to manipulate a central pathway essential for the development of metazoans and often deregulated in illnesses such as stroke, cancer or cardiovascular diseases. Commonly, the Notch cascade is inhibited by small compound inhibitors, which either block the proteolysis of Notch receptors by γ-secretases or interfere with the transcriptional activity of the Notch intracellular domain. Specific antibodies can also be used to inhibit ligand-induced activation of Notch receptors. Alternatively, naturally occurring endogenous inhibitors of Notch signalling might offer a specific way to block receptor activation. Examples are the soluble variants of the canonical Notch ligand Jagged1 and the non-canonical Notch ligand Dlk1, both deprived of their transmembrane regions upon ectodomain shedding, or the bona fide secreted molecule EGFL7. We present frequently used methods to decrease Notch signalling, and we discuss how soluble Notch inhibitors may be used to treat diseases.