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↑, NPL4↓,
6739- DSF,    Disulfiram's anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase
- in-vitro, Lung, H1299 - in-vitro, Lung, A549
ALDH↓, eff↝, NPL4↓,
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↓, other↝, DNAdam↑,
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↓, P53↑,
6742- DSF,    Localized Sustained Release of Copper Enhances Anti-Tumor Effects of Disulfiram in Head and Neck Cancer
- in-vitro, HNSCC, NA
TumCG↓, NPL4↓,

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=0  sortOrder:rid,rpid

 

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