biostudies-literatureJin BNCI NIH HHS14356-65https://www.ebi.ac.uk/biostudies/studies/S-EPMC2863211biostudies-literatureUnknown285(19)Nuclear factor-kappaB (NF-kappaB)-based signaling regulates diverse biological processes, and its deregulation is associated with various disorders including autoimmune diseases and cancer. Identification of novel factors that modulate NF-kappaB function is therefore of significant importance. The Mastermind-like 1 (MAML1) transcriptional co-activator regulates transcriptional activity in the Notch pathway and is emerging as a co-activator of other pathways. In this study, we found that MAML1 regulates NF-kappaB signaling via two mechanisms. First, MAML1 co-activates the NF-kappaB subunit RelA (p65) in NF-kappaB-dependent transcription. Second, MAML1 causes degradation of the inhibitor of NF-kappaB (IkappaBalpha). Maml1-deficient mouse embryonic fibroblasts showed impaired tumor necrosis fThe Journal of biological chemistryThe mastermind-like 1 (MAML1) co-activator regulates constitutive NF-kappaB signaling and cell survival.PMC2863211R01 CA036167R01 CA097148Griffin JDWu LLin SJin BChen ZLi JLShen HfalseThe mastermind-like 1 (MAML1) co-activator regulates constitutive NF-kappaB signaling and cell survival.Nuclear factor-kappaB (NF-kappaB)-based signaling regulates diverse biological processes, and its deregulation is associated with various disorders including autoimmune diseases and cancer. Identification of novel factors that modulate NF-kappaB function is therefore of significant importance. The Mastermind-like 1 (MAML1) transcriptional co-activator regulates transcriptional activity in the Notch pathway and is emerging as a co-activator of other pathways. In this study, we found that MAML1 regulates NF-kappaB signaling via two mechanisms. First, MAML1 co-activates the NF-kappaB subunit RelA (p65) in NF-kappaB-dependent transcription. Second, MAML1 causes degradation of the inhibitor of NF-kappaB (IkappaBalpha). Maml1-deficient mouse embryonic fibroblasts showed impaired tumor necrosis f2010-01-01T00:00:00Z2010 May2025-04-04T11:56:11.543Z2019-03-27T00:30:30ZS-EPMC28632112023127810.1074/jbc.m109.07886510.1074/jbc.M109.078865