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 journalArticle

6 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 languageEnglish (US)
Pages (from-to)3647-3656
Number of pages10
JournalOncogene
Volume37
Issue number27
DOIs
StatePublished - Jul 5 2018

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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