NPL4 Cancer Research Results

NPL4, NPLOC4: Click to Expand ⟱
Source:
Type:

NPL4 is not an enzyme itself. It is a ubiquitin-recognition adaptor that works with UFD1 and VCP/p97 to extract ubiquitinated proteins from membranes, chromatin and protein complexes for processing or proteasomal degradation. It is involved in ER-associated degradation, DNA replication, DNA repair and mitotic functions.

In cancer, NPL4/NPLOC4 is generally considered tumour-promoting when increased or active.

Disulfiram modulates NPL4 in the inhibitory direction:

Disulfiram + copper → NPL4 aggregation/immobilization → NPL4 function ↓

More precisely, disulfiram is converted to diethyldithiocarbamate, which complexes with copper to form CuET [Cu(DDC)₂]. 
CuET binds to NPL4 and causes it to cluster into insoluble aggregates. 
This disables NPL4 as an adaptor of the VCP/p97–UFD1–NPL4 segregase complex


Scientific Papers found: Click to Expand⟱
6738- DSF,    Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
- Review, Var, NA
eff↑, We propose a model for DSF cytotoxic activity, featuring rapid conversion of DSF into CuET which accumulates in tumours.
NPL4↓, After entering cells CuET binds NPL4 and induces its aggregation, consequently disabling the vital p97-NPL4-UFD1 pathway and inducing a complex cellular phenotype leading to cell death

6742- DSF,    Localized Sustained Release of Copper Enhances Anti-Tumor Effects of Disulfiram in Head and Neck Cancer
- in-vitro, HNSCC, NA
TumCG↓, The combination of DSF and copper could achieve a tumor cell growth inhibition effect comparable to that of 5-fluorouracil and taxol on head and neck cancer cells.
NPL4↓, molecular target of DSF’s tumor-suppressing effects is NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells

6741- DSF,    Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET
- vitro+vivo, Lung, A549
NPL4↓, We have recently reported that the disulfiram metabolite diethyldithiocarbamate, when combined with copper (CuET), targets the NPL4 adapter of the p97VCP segregase to suppress the growth of a spectrum of cancer cell lines and xenograft models in vivo
P53↑, We previously reported that CuET induces a higher p53 protein level in human cells irrespective of their p53 genetic status

6740- DSF,    Targeting the NPL4 Adaptor of p97/VCP Segregase by Disulfiram as an Emerging Cancer Vulnerability Evokes Replication Stress and DNA Damage while Silencing the ATR Pathway
NPL4↓, Research on repurposing the old alcohol-aversion drug disulfiram (DSF) for cancer treatment has identified inhibition of NPL4, an adaptor of the p97/VCP segregase essential for turnover of proteins involved in multiple pathways, as an unsuspected can
other↝, NPL4 is targeted by the anticancer metabolite of DSF, the bis-diethyldithiocarbamate-copper complex (CuET), the exact, apparently multifaceted mechanism(s) through which the CuET-induced aggregation of NPL4 kills cancer cells remains to be fully eluc
DNAdam↑, CuET Causes DNA Damage Preferentially Detectable in S/G2-Phase Cells

6739- DSF,    Disulfiram's anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase
- in-vitro, Lung, H1299 - in-vitro, Lung, A549
ALDH↓, ALDH inhibition as a treatment approach is supported by anti-cancer effects of the alcohol-abuse drug disulfiram (DSF, Antabuse).
eff↝, Given that metabolic products of DSF, rather than DSF itself inhibit ALDH in vivo, and that DSF's anti-cancer activity is potentiated by copper led us to investigate the relevance of ALDH as the suggested molecular cancer-relevant target of DSF
NPL4↓, kills cells through aggregation of NPL4, a subunit of the p97/VCP segregase.


Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

NPL4↓, 5,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ALDH↓, 1,   TumCG↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,   eff↝, 1,  
Total Targets: 8

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: NPL4, NPLOC4
5 Disulfiram
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1526  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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