| 1. |
- Chapman, G, et al.
(författare)
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High levels of Notch signaling down-regulate Numb and Numblike
- 2006
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 175:4, s. 535-540
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch, high levels of Notch signaling conversely led to a reduction of Numb and Numblike protein levels in cultured cells and in the developing chick central nervous system. The Notch intracellular domain but not the canonical Notch downstream proteins Hes 1 and Hey 1 caused a reduction of Numb and Numblike. The Notch-mediated reduction of Numblike required the PEST domain in the Numblike protein and was blocked by the proteasome inhibitor MG132. Collectively, these observations reveal a reciprocal negative regulation between Notch and Numb/Numblike, which may be of relevance for stabilizing asymmetric cell fate switches and for tumor development.
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| 2. |
- Sahlgren, C, et al.
(författare)
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Notch signaling and its integration with other signaling mechanisms
- 2006
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Ingår i: Regenerative medicine. - : Future Medicine Ltd. - 1746-076X .- 1746-0751. ; 1:2, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- An improved understanding of stem cell differentiation is critical for progress in regenerative medicine. It is an emerging view that a relatively small number of intracellular signaling mechanisms play particularly important roles in differentiation control. As one may expect, these pathways are highly evolutionarily conserved, used in many tissues and iteratively during differentiation of a particular tissue. The Notch signaling system is one pathway meeting these criteria. In many cases, Notch signaling keeps stem/progenitor cells undifferentiated, although it can in some cellular contexts be instructive for differentiation toward a particular fate. Here, we review our current understanding of how Notch controls cellular differentiation in various organs and how Notch integrates with other major signaling pathways, primarily focusing on Notch signaling in mammals. Given the importance of Notch in many stem cell fate decisions, the possibility of experimentally manipulating Notch signaling opens up new avenues to control stem cell differentiation.
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