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Notch1 activation reduces proliferation in the multipotent hematopoietic progenitor cell line FDCP-mix through a p53-dependent pathway but Notch1 effects on myeloid and erythroid differentiation are independent of p53.
- Source :
-
Cell Death & Differentiation . Feb2008, Vol. 15 Issue 2, p398-407. 10p. 1 Black and White Photograph, 3 Charts, 5 Graphs. - Publication Year :
- 2008
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Abstract
- Signaling mediated by activation of the transmembrane receptor Notch influences cell-fate decisions, differentiation, proliferation, and cell survival. Activated Notch reduces proliferation by altering cell-cycle kinetics and promotes differentiation in hematopoietic progenitor cells. Here, we investigated if the G1 arrest and differentiation induced by activated mNotch1 are dependent on tumor suppressor p53, a critical mediator of cellular growth arrest. Multipotent wild-type p53-expressing (p53wt) and p53-deficient (p53null) hematopoietic progenitor cell lines (FDCP-mix) carrying an inducible mNotch1 system were used to investigate the effects of proliferation and differentiation upon mNotch1 signaling. While activated Notch reduced proliferation of p53wt-cells, no change was observed in p53null-cells. Activated Notch upregulated the p53 target p21cip/waf in p53wt-cells, but not in p53null-cells. Induction of the p21cip/waf gene by activated Notch was mediated by increased binding of p53 to p53-binding sites in the p21cip/waf promoter and was independent of the canonical RBP-J binding site. Re-expression of p53wt in p53null cells restored the inhibition of proliferation by activated Notch. Thus, activated Notch inhibits proliferation of multipotent hematopoietic progenitor cells via a p53-dependent pathway. In contrast, myeloid and erythroid differentiation was similarly induced in p53wt and p53null cells. These data suggest that Notch signaling triggers two distinct pathways, a p53-dependent one leading to a block in proliferation and a p53-independent one promoting differentiation.Cell Death and Differentiation (2008) 15, 398–407; doi:10.1038/sj.cdd.4402277; published online 30 November 2007 [ABSTRACT FROM AUTHOR]
- Subjects :
- *NOTCH genes
*CELL differentiation
*MORPHOGENESIS
*ERYTHROCYTE membranes
*CYTOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 15
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 28438413
- Full Text :
- https://doi.org/10.1038/sj.cdd.4402277