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Science 314 (5804): 1414-1415

Copyright © 2006 by the American Association for the Advancement of Science

Notch, a Universal Arbiter of Cell Fate Decisions

Matthias Ehebauer,1 Penelope Hayward,2 Alfonso Martinez Arias2*

Abstract: Members of the Notch family of receptors act as membrane-tethered transcription factors that are tightly associated with binary cell fate decisions. Notch signaling acts as a molecular gate that allows cells to adopt or forfeit a particular fate. Interaction of Notch with ligands triggers a sequence of proteolytic cleavages that release the intracellular domain to the nucleus; this mechanism is a target of therapies for leukemias associated with Notch activation. Although the molecular mechanism of Notch activation is well characterized, further analysis in an appropriate cellular context will provide new insight into Notch signaling.

1 Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
2 Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.

* To whom correspondence should be addressed. E-mail: ama11{at}

Renal tubular Notch signaling triggers a prosenescent state after acute kidney injury.
I. Sorensen-Zender, S. Rong, N. Susnik, S. Zender, P. Pennekamp, A. Melk, H. Haller, and R. Schmitt (2014)
Am J Physiol Renal Physiol 306, F907-F915
   Abstract »    Full Text »    PDF »
A Protein (ORF2) Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 Interacts with DNA.
D. Pittayakhajonwut, D. Sinani, and C. Jones (2013)
J. Virol. 87, 5493-5501
   Abstract »    Full Text »    PDF »
Changes of number of cells expressing proliferation and progenitor cell markers with age in rabbit intervertebral discs.
M. Yasen, Q. Fei, W. C. Hutton, J. Zhang, J. Dong, X. Jiang, and F. Zhang (2013)
Acta Biochim Biophys Sin 45, 368-376
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Cross-talk between leukemic and endothelial cells promotes angiogenesis by VEGF activation of the Notch/Dll4 pathway.
J. Zhang, J. Ye, D. Ma, N. Liu, H. Wu, S. Yu, X. Sun, W. Tse, and C. Ji (2013)
Carcinogenesis 34, 667-677
   Abstract »    Full Text »    PDF »
A Bovine Herpesvirus 1 Protein Expressed in Latently Infected Neurons (ORF2) Promotes Neurite Sprouting in the Presence of Activated Notch1 or Notch3.
D. Sinani, L. Frizzo da Silva, and C. Jones (2013)
J. Virol. 87, 1183-1192
   Abstract »    Full Text »    PDF »
cAMP-responsive Element Modulator {alpha} (CREM{alpha}) Contributes to Decreased Notch-1 Expression in T Cells from Patients with Active Systemic Lupus Erythematosus (SLE).
T. Rauen, A. P. Grammatikos, C. M. Hedrich, J. Floege, K. Tenbrock, K. Ohl, V. C. Kyttaris, and G. C. Tsokos (2012)
J. Biol. Chem. 287, 42525-42532
   Abstract »    Full Text »    PDF »
Reciprocal Interaction between TRAF6 and Notch Signaling Regulates Adult Myofiber Regeneration upon Injury.
S. M. Hindi, P. K. Paul, S. Dahiya, V. Mishra, S. Bhatnagar, S. Kuang, Y. Choi, and A. Kumar (2012)
Mol. Cell. Biol. 32, 4833-4845
   Abstract »    Full Text »    PDF »
The Endocannabinoid, Anandamide, Augments Notch-1 Signaling in Cultured Cortical Neurons Exposed to Amyloid-{beta} and in the Cortex of Aged Rats.
R. Tanveer, A. Gowran, J. Noonan, S. E. Keating, A. G. Bowie, and V. A. Campbell (2012)
J. Biol. Chem. 287, 34709-34721
   Abstract »    Full Text »    PDF »
Notch system in the linkage of innate and adaptive immunity.
T. Ito, J. M. Connett, S. L. Kunkel, and A. Matsukawa (2012)
J. Leukoc. Biol. 92, 59-65
   Abstract »    Full Text »    PDF »
TNF{alpha} inhibitors restrict T cell activation and cycling via Notch-1 signalling in inflammatory bowel disease.
L. Werner, U. Berndt, D. Paclik, S. Danese, A. Schirbel, and A. Sturm (2012)
Gut 61, 1016-1027
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Cellular Transcription Factors Induced in Trigeminal Ganglia during Dexamethasone-Induced Reactivation from Latency Stimulate Bovine Herpesvirus 1 Productive Infection and Certain Viral Promoters.
A. Workman, J. Eudy, L. Smith, L. Frizzo da Silva, D. Sinani, H. Bricker, E. Cook, A. Doster, and C. Jones (2012)
J. Virol. 86, 2459-2473
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Localization of Sequences in a Protein (ORF2) Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 That Inhibits Apoptosis and Interferes with Notch1-Mediated trans-Activation of the bICP0 Promoter.
D. Sinani and C. Jones (2011)
J. Virol. 85, 12124-12133
   Abstract »    Full Text »    PDF »
A Protein (ORF2) Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 Interacts with Notch1 and Notch3.
A. Workman, D. Sinani, D. Pittayakhajonwut, and C. Jones (2011)
J. Virol. 85, 2536-2546
   Abstract »    Full Text »    PDF »
NOTCH, a new signaling pathway implicated in holoprosencephaly.
V. Dupe, L. Rochard, S. Mercier, Y. Le Petillon, I. Gicquel, C. Bendavid, G. Bourrouillou, U. Kini, C. Thauvin-Robinet, T. P. Bohan, et al. (2011)
Hum. Mol. Genet. 20, 1122-1131
   Abstract »    Full Text »    PDF »
Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome.
J. J. Hofmann, A. C. Zovein, H. Koh, F. Radtke, G. Weinmaster, and M. L. Iruela-Arispe (2010)
Development 137, 4061-4072
   Abstract »    Full Text »    PDF »
Notch Exhibits Ligand Bias and Maneuvers Stage-Specific Steering of Neural Differentiation in Embryonic Stem Cells.
S. K. Ramasamy and N. Lenka (2010)
Mol. Cell. Biol. 30, 1946-1957
   Abstract »    Full Text »    PDF »
Notch-1 Inhibition by Withaferin-A: A Therapeutic Target against Colon Carcinogenesis.
S. Koduru, R. Kumar, S. Srinivasan, M. B. Evers, and C. Damodaran (2010)
Mol. Cancer Ther. 9, 202-210
   Abstract »    Full Text »    PDF »
Regulatory T Cells Negatively Regulate Neovasculature of Airway Remodeling via DLL4-Notch Signaling.
M.-T. Huang, Y.-S. Dai, Y.-B. Chou, Y.-H. Juan, C.-C. Wang, and B.-L. Chiang (2009)
J. Immunol. 183, 4745-4754
   Abstract »    Full Text »    PDF »
Notch signaling controls liver development by regulating biliary differentiation.
Y. Zong, A. Panikkar, J. Xu, A. Antoniou, P. Raynaud, F. Lemaigre, and B. Z. Stanger (2009)
Development 136, 1727-1739
   Abstract »    Full Text »    PDF »
Simvastatin Increases Notch Signaling Activity and Promotes Arteriogenesis After Stroke.
A. Zacharek, J. Chen, X. Cui, Y. Yang, and M. Chopp (2009)
Stroke 40, 254-260
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HES-1 Is Involved in Adaptation of Adult Human {beta}-Cells to Proliferation In Vitro.
Y. Bar, H. A. Russ, S. Knoller, L. Ouziel-Yahalom, and S. Efrat (2008)
Diabetes 57, 2413-2420
   Abstract »    Full Text »    PDF »
Crosstalk Between Vascular Endothelial Growth Factor, Notch, and Transforming Growth Factor-{beta} in Vascular Morphogenesis.
M. T. Holderfield and C. C.W. Hughes (2008)
Circ. Res. 102, 637-652
   Abstract »    Full Text »    PDF »
Wnt/Notch signalling and information processing during development.
P. Hayward, T. Kalmar, and A. Martinez Arias (2008)
Development 135, 411-424
   Abstract »    Full Text »    PDF »
Notch signaling induces cytoplasmic CD3{epsilon} expression in human differentiating NK cells.
M. De Smedt, T. Taghon, I. Van de Walle, G. De Smet, G. Leclercq, and J. Plum (2007)
Blood 110, 2696-2703
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Genetic Background Modifies Inner Ear and Eye Phenotypes of Jag1 Heterozygous Mice.
A. E. Kiernan, R. Li, N. L. Hawes, G. A. Churchill, and T. Gridley (2007)
Genetics 177, 307-311
   Abstract »    Full Text »    PDF »
Notch signaling in vascular development and physiology.
T. Gridley (2007)
Development 134, 2709-2718
   Abstract »    Full Text »    PDF »

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