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The mastermind-like 1 (MAML1) co-activator regulates constitutive NF-kappaB signaling and cell survival.


ABSTRACT: 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 factor-alpha (TNFalpha)-induced NF-kappaB responses. Moreover, MAML1 expression level directly influences cellular sensitivity to TNFalpha-induced cytotoxicity. In vivo, mice deficient in the Maml1 gene exhibited spontaneous cell death in the liver, with a large increase in the number of apoptotic hepatic cells. These findings indicate that MAML1 is a novel modulator for NF-kappaB signaling and regulates cellular survival.

SUBMITTER: Jin B 

PROVIDER: S-EPMC2863211 | biostudies-other | 2010 May

REPOSITORIES: biostudies-other

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The mastermind-like 1 (MAML1) co-activator regulates constitutive NF-kappaB signaling and cell survival.

Jin Baofeng B   Shen Huangxuan H   Lin Shuibin S   Li Jian-Liang JL   Chen Zirong Z   Griffin James D JD   Wu Lizi L  

The Journal of biological chemistry 20100315 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 re  ...[more]

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