NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation

Claudia M. Nicolae; Michael J. O'connor; Daniel Constantin; George Lucian Moldovan

doi:10.1038/s41388-018-0219-y

NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation

Claudia M. Nicolae, Michael J. O'connor, Daniel Constantin, George Lucian Moldovan

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells. In order to understand the role of this unexpected regulatory event, we ablated the NFκB binding site we identified in the p21 promoter, using CRISPR/Cas9-mediated genome editing. We found that NFκB-mediated p21 activation controls DNA damage-induced myeloid differentiation. Our results uncover a p53-independent pathway for p21 activation involved in controlling hematopoietic cell fate.

Original language	English (US)
Pages (from-to)	3647-3656
Number of pages	10
Journal	Oncogene
Volume	37
Issue number	27
DOIs	https://doi.org/10.1038/s41388-018-0219-y
State	Published - Jul 5 2018

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cancer Research

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10.1038/s41388-018-0219-y

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title = "NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation",

abstract = "DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells. In order to understand the role of this unexpected regulatory event, we ablated the NFκB binding site we identified in the p21 promoter, using CRISPR/Cas9-mediated genome editing. We found that NFκB-mediated p21 activation controls DNA damage-induced myeloid differentiation. Our results uncover a p53-independent pathway for p21 activation involved in controlling hematopoietic cell fate.",

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AU - Nicolae, Claudia M.

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AU - Constantin, Daniel

AU - Moldovan, George Lucian

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N2 - DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells. In order to understand the role of this unexpected regulatory event, we ablated the NFκB binding site we identified in the p21 promoter, using CRISPR/Cas9-mediated genome editing. We found that NFκB-mediated p21 activation controls DNA damage-induced myeloid differentiation. Our results uncover a p53-independent pathway for p21 activation involved in controlling hematopoietic cell fate.

AB - DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells. In order to understand the role of this unexpected regulatory event, we ablated the NFκB binding site we identified in the p21 promoter, using CRISPR/Cas9-mediated genome editing. We found that NFκB-mediated p21 activation controls DNA damage-induced myeloid differentiation. Our results uncover a p53-independent pathway for p21 activation involved in controlling hematopoietic cell fate.

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NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation

Abstract

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