The Death Domain of NF-κB1 p105 Is Essential for Signal-induced p105 Proteolysis

IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell–dependent antigen

The importance of IκB kinase (IKK)-induced proteolysis of NF-κB1 p105 in B cells was investigated using Nfkb1(SSAA/SSAA) mice, in which this NF-κB signaling pathway is blocked. Nfkb1(SSAA) mutation had no effect on the development and homeostasis of follicular mature (FM) B cells. However, analysis of mixed bone marrow chimeras revealed that Nfkb1(SSAA/SSAA) FM B cells were completely unable to...

TrCP-mediated proteolysis of NF-�B1 p105 requires phosphorylation of p105 serines 927

KPC1-Mediated Ubiquitination and Proteasomal Processing of NF-κB1 p105 to p50 Restricts Tumor Growth

NF-κB is a key transcriptional regulator involved in inflammation and cell proliferation, survival, and transformation. Several key steps in its activation are mediated by the ubiquitin (Ub) system. One uncharacterized step is limited proteasomal processing of the NF-κB1 precursor p105 to the p50 active subunit. Here, we identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats doma...

Lack of NF-κB1 (p105/p50) attenuates unloading-induced downregulation of PPARα and PPARα-regulated gene expression in rodent heart

Objective: Unloading of the rodent heart activates the fetal gene program, decreases peroxisome proliferator-activated receptor α (PPARα) and PPARα-regulated gene expression (MCAD), and induces cardiomyocyte atrophy. NF-κB regulates the fetal gene program and PPARαregulated gene expression during cardiac hypertrophy and induces atrophy in skeletal muscle. Our objective was to test the hypothesi...

Quantitative dissection and modeling of the NF-κB p100-p105 module reveals interdependent precursor proteolysis.

The mechanisms that govern proteolytic maturation or complete destruction of the precursor proteins p100 and p105 are fundamental to homeostasis and activation of NF-κB; however, they remain poorly understood. Using mass-spectrometry-based quantitative analysis of noncanonical LTβR-induced signaling, we demonstrate that stimulation induces simultaneous processing of both p100 and p105. The prec...