Document Type
Article
Publication Date
9-16-2020
Abstract
Notch signaling regulates squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is tumor suppressive. Here, we show that conditional activation of Notch in squamous cells activates a context-specific gene expression program through lineage-specific regulatory elements. Among direct Notch target genes are multiple DNA damage response genes, including IER5, which we show is required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes. IER5 is epistatic to PPP2R2A, a gene that encodes the PP2A B55α subunit, which we show interacts with IER5 in cells and in purified systems. Thus, Notch and DNA-damage response pathways converge in squamous cells on common genes that promote differentiation, which may serve to eliminate damaged cells from the proliferative pool. We further propose that crosstalk involving Notch and PP2A enables tuning and integration of Notch signaling with other pathways that regulate squamous differentiation.
Recommended Citation
Pan, Li; Lemieux, Madeleine E; Thomas, Tom; Rogers, Julia M; Lipper, Colin H; Lee, Winston; Johnson, Carl; Sholl, Lynette M; South, Andrew P.; Marto, Jarrod A; Adelmant, Guillaume O; Blacklow, Stephen C; and Aster, Jon C, "IER5, a dna damage response gene, is required for notch-mediated induction of squamous cell differentiation" (2020). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 138.
https://jdc.jefferson.edu/dcbfp/138
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
32936072
Language
English
Comments
This article is the author’s final published version in eLife, Volume 9, September 2020, Article number e58081.
The published version is available at https://doi.org/10.7554/eLife.58081. Copyright © Pan et al.