ArticleThe Journal of biological chemistry2015
The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The polymerized protein response (PPR) is activated by genetic variants that polymerize in the ER and is mediated by NFκBp50.Nature communications · 2026Article
- Comparison of MicroalgaeMarine drugs · 2024Article
- Article
- Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- iTRAQ-Based Proteomic Profile Analysis of the Hepatopancreas of Caribbean Spiny Lobsters Infected WithFrontiers in microbiology · 2020Article
- Interactions of the super complexes: When mTORC1 meets the proteasome.The international journal of biochemistry & cell biology · 2019Review
- Valosin-containing protein promotes metastasis of osteosarcoma through autophagy induction and anoikis inhibition via the ERK/NF-κβ/beclin-1 signaling pathway.Oncology letters · 2019Article
- Upregulation of NPL4 promotes bladder cancer cell proliferation by inhibiting DXO destabilization of cyclin D1 mRNA.Cancer cell international · 2019Article
- Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function.EMBO reports · 2018Article
- Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila melanogaster.Journal of genetics and genomics = Yi chuan xue bao · 2017Article
- Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP•NPLOC4•UFD1L is enhanced by a mutation that causes multisystem proteinopathy.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- p97 Negatively Regulates NRF2 by Extracting Ubiquitylated NRF2 from the KEAP1-CUL3 E3 Complex.Molecular and cellular biology · 2017Article
- A Mighty "Protein Extractor" of the Cell: Structure and Function of the p97/CDC48 ATPase.Frontiers in molecular biosciences · 2017Review
- Targeting p97 to Disrupt Protein Homeostasis in Cancer.Frontiers in oncology · 2016Review
- Article
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Authors and funding
10 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.