jrf-12 and Pneumonia

jrf-12 has been researched along with Pneumonia* in 1 studies

Other Studies

1 other study(ies) available for jrf-12 and Pneumonia

ArticleYear
The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100.
    The Journal of biological chemistry, 2015, Aug-07, Volume: 290, Issue:32

    Partial degradation of the p100 subunit to generate p52 subunit is a hallmark of the alternative NF-κB pathway, which has been implicated in cancer. Here, we uncovered a role of the p97-Npl4-Ufd1 complex in mediating p100-to-p52 processing and therefore positively regulating the alternative NF-κB pathway. We observed an elevation of p97 mRNA levels in lymphoma patients, which positively correlates with NFKB2 expression, a downstream target gene of the alternative NF-κB pathway. Moreover, NFKB2 mRNA levels were aberrantly down-regulated in patients with inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD), a disease caused by mutation of p97. Inactivation of p97 or depletion of the p97-Npl4-Ufd1 complex inhibits the processing of p100 into p52, decreasing transcription of the downstream target genes. Further analyses reveal that the p97-Npl4-Ufd1 complex interacts with F-box and WD repeats protein SCF(βTrCP) complex to regulate the partial degradation of p100, a process involving K48- and K11-linked ubiquitination. In line with this, in LPS-induced lung damage mice model, generation of p52 is significantly decreased in p97-KD mice compared with mock mice. Finally, abrogation of p97 ATPase activity by its specific inhibitor DBeQ, efficiently decreased proliferation of lymphoma cells. Collectively, our study revealed a regulatory role of the p97-Npl4-Ufd1 complex in regulating p100 partial degradation, highlighting the potential of p97 as a drug target for cancers with aberrant activation of the alternative NF-κB pathway.

    Topics: Adaptor Proteins, Vesicular Transport; Animals; beta Karyopherins; Cell Line, Tumor; Endoplasmic Reticulum; Fibroblasts; Gene Expression Regulation; HEK293 Cells; Humans; Intracellular Signaling Peptides and Proteins; Lipopolysaccharides; Lung; Lymphocytes; Male; Mice; Mice, Knockout; NF-kappa B p52 Subunit; Nuclear Proteins; Pneumonia; Proteasome Endopeptidase Complex; Proteins; Proteolysis; Quinazolines; Signal Transduction; SKP Cullin F-Box Protein Ligases; Transcription, Genetic; Ubiquitination

2015