Decoding the PTM-switchboard of Notch.
Biochim Biophys Acta Mol Cell Res
; 1866(12): 118507, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31301363
ABSTRACT
The developmentally indispensable Notch pathway exhibits a high grade of pleiotropism in its biological output. Emerging evidence supports the notion of post-translational modifications (PTMs) as a modus operandi controlling dynamic fine-tuning of Notch activity. Although, the intricacy of Notch post-translational regulation, as well as how these modifications lead to multiples of divergent Notch phenotypes is still largely unknown, numerous studies show a correlation between the site of modification and the output. These include glycosylation of the extracellular domain of Notch modulating ligand binding, and phosphorylation of the PEST domain controlling half-life of the intracellular domain of Notch. Furthermore, several reports show that multiple PTMs can act in concert, or compete for the same sites to drive opposite outputs. However, further investigation of the complex PTM crosstalk is required for a complete understanding of the PTM-mediated Notch switchboard. In this review, we aim to provide a consistent and up-to-date summary of the currently known PTMs acting on the Notch signaling pathway, their functions in different contexts, as well as explore their implications in physiology and disease. Furthermore, we give an overview of the present state of PTM research methodology, and allude to a future with PTM-targeted Notch therapeutics.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Notch
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Ano de publicação:
2019
Tipo de documento:
Article