biostudies-literatureGlynn RAHHS | NIH | National Institute of General Medical SciencesNIAID NIH HHSHHS | NIH | National Institute of Allergy and Infectious DiseasesNIGMS NIH HHSHHS | NIH | National Institute of General Medical Sciences (NIGMS)HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)628-640https://www.ebi.ac.uk/biostudies/studies/S-EPMC11348802biostudies-literatureUnknown213(5)In response to DNA double-strand breaks (DSBs), the ATM kinase activates NF-κB factors to stimulate gene expression changes that promote survival and allow time for cells to repair damage. In cell lines, ATM can activate NF-κB transcription factors via two independent, convergent mechanisms. One is ATM-mediated phosphorylation of nuclear NF-κB essential modulator (Nemo) protein, which leads to monoubiquitylation and export of Nemo to the cytoplasm where it engages the IκB kinase (IKK) complex to activate NF-κB. Another is DSB-triggered migration of ATM into the cytoplasm, where it promotes monoubiquitylation of Nemo and the resulting IKK-mediated activation of NF-κB. ATM has many other functions in the DSB response beyond activation of NF-κB, and Nemo activates NF-κB downstream of diverse Journal of immunology (Baltimore, Md. : 1950)ATM-dependent Phosphorylation of Nemo SQ Motifs Is Dispensable for Nemo-mediated Gene Expression Changes in Response to DNA Double-Strand Breaks.PMC11348802T32 GM-07229R01 AI172163R01 AI 130231R01 AI112621R01 AI 172163F31 AI 152354F31 AI152354R01 AI143661R01 AI130231T32 GM007229R01 AI 112621Hayer KEGlynn RABassing CHfalseATM-dependent Phosphorylation of Nemo SQ Motifs Is Dispensable for Nemo-mediated Gene Expression Changes in Response to DNA Double-Strand Breaks.In response to DNA double-strand breaks (DSBs), the ATM kinase activates NF-κB factors to stimulate gene expression changes that promote survival and allow time for cells to repair damage. In cell lines, ATM can activate NF-κB transcription factors via two independent, convergent mechanisms. One is ATM-mediated phosphorylation of nuclear NF-κB essential modulator (Nemo) protein, which leads to monoubiquitylation and export of Nemo to the cytoplasm where it engages the IκB kinase (IKK) complex to activate NF-κB. Another is DSB-triggered migration of ATM into the cytoplasm, where it promotes monoubiquitylation of Nemo and the resulting IKK-mediated activation of NF-κB. ATM has many other functions in the DSB response beyond activation of NF-κB, and Nemo activates NF-κB downstream of diverse 2024-01-01T00:00:00Z2024 Sep2026-07-15T12:47:49.345Z2026-07-04T03:16:08.774ZS-EPMC113488023900764110.4049/jimmunol.2300139