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IER5, a DNA damage response gene, is required for Notch-mediated induction of squamous cell differentiation

التفاصيل البيبلوغرافية
العنوان: IER5, a DNA damage response gene, is required for Notch-mediated induction of squamous cell differentiation
المؤلفون: Li Pan, Madeleine E Lemieux, Tom Thomas, Julia M Rogers, Colin H Lipper, Winston Lee, Carl Johnson, Lynette M Sholl, Andrew P South, Jarrod A Marto, Guillaume O Adelmant, Stephen C Blacklow, Jon C Aster
المصدر: eLife, Vol 9 (2020)
بيانات النشر: eLife Sciences Publications Ltd, 2020.
سنة النشر: 2020
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: Notch, PP2A, DNA damage response, squamous cell carcinoma, Medicine, Science, Biology (General), QH301-705.5
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/58081; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.58081
URL الوصول: https://doaj.org/article/ae52c805774448d4bf9d92c9ea73aab9
رقم الأكسشن: edsdoj.52c805774448d4bf9d92c9ea73aab9
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.58081