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.

Majera, Dusana; Skrott, Zdenek; Chroma, Katarina; Merchut-Maya, Joanna Maria; Mistrik, Martin; Bartek, Jiri

Majera, Dusana; Skrott, Zdenek; Chroma, Katarina; Merchut-Maya, Joanna Maria; Mistrik, Martin; Bartek, Jiri.

Affiliation

Majera D; Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77 147 Olomouc, Czech Republic.
Skrott Z; Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77 147 Olomouc, Czech Republic.
Chroma K; Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77 147 Olomouc, Czech Republic.
Merchut-Maya JM; Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.
Mistrik M; Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77 147 Olomouc, Czech Republic.
Bartek J; Laboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77 147 Olomouc, Czech Republic.

Cells ; 9(2)2020 02 18.

Article in En | MEDLINE | ID: mdl-32085572

Subject(s)

Alcohol Deterrents/pharmacology; Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors; DNA Damage/drug effects; DNA Replication/drug effects; Disulfiram/pharmacology; Neoplasms/metabolism; Nuclear Proteins/antagonists & inhibitors; Adaptor Proteins, Signal Transducing/metabolism; Ataxia Telangiectasia Mutated Proteins/metabolism; Cell Line, Tumor; Checkpoint Kinase 1/metabolism; DNA-Binding Proteins/metabolism; Humans; Neoplasms/pathology; Nuclear Proteins/metabolism; Protein Aggregates/drug effects; Protein Aggregation, Pathological/chemically induced; Signal Transduction/drug effects; Valosin Containing Protein/metabolism

Key words

ATR pathway; BRCA1; BRCA2; DNA damage; NPL4; disulfiram; replication stress; targeted cancer therapy

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Full text: 1 Database: MEDLINE Main subject: DNA Damage / Nuclear Proteins / Disulfiram / Alcohol Deterrents / DNA Replication / Ataxia Telangiectasia Mutated Proteins / Neoplasms Language: En Journal: Cells Year: 2020 Type: Article Affiliation country: Czech Republic

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