Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1863, Issue 2, Pages 303-313Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2015.11.020
Keywords
Notch signal transduction, Post-translational modifications; Methylation, Hydroxylation, Signaling crosstalk, Transcription factor Hes1; Transcription factor Hes1
Categories
Funding
- Heisenberg program [BO 1639/5-1]
- DFG (German Research Foundation)
- University Medical Center Giessen and Marburg (UKGM)
- DFG [SFB 1074/A3]
- BMBF (Federal Ministry of Education and Research, research nucleus SyStAR)
- Erasmus MC
- [TRR81/A12]
- [FWO-VG.0542.13]
- [GOA11/012]
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Notch signaling is a highly conserved signal transduction pathway that regulates stem cell maintenance and differentiation in several organ systems. Upon activation, the Notch receptor is proteolytically processed, its intracellular domain (NICD) translocates into the nucleus and activates expression of target genes. Output, strength and duration of the signal are tightly regulated by post-translational modifications. Here we review the intracellular post-translational regulation of Notch that fine-tunes the outcome of the Notch response. We also describe how crosstalk with other conserved signaling pathways like the Wnt, Hedgehog, hypoxia and TGF beta/BMP pathways can affect Notch signaling output. This regulation can happen by regulation of ligand, receptor or transcription factor expression, regulation of protein stability of intracellular key components, usage of the same cofactors or coregulation of the same key target genes. Since carcinogenesis is often dependent on at least two of these pathways, a better understanding of their molecular crosstalk is pivotal. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
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