The Ubiquitin Ligase TRIP12 Limits PARP1 Trapping and Constrains PARP Inhibitor Efficiency

PARP inhibitors (PARPi) cause synthetic lethality in BRCA-deficient tumors. Whether specific vulnerabilities to PARPi exist beyond BRCA mutations and related defects in homology-directed repair (HDR) is not well understood. Here, we identify the ubiquitin E3 ligase TRIP12 as negative regulator of PA...

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Veröffentlicht in:	Cell reports (Cambridge) Jg. 32; H. 5; S. 107985
Hauptverfasser:	Gatti, Marco, Imhof, Ralph, Huang, Qingyao, Baudis, Michael, Altmeyer, Matthias
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Elsevier Inc 04.08.2020 Cell Press Elsevier
Schlagworte:	Amino Acid Sequence BRCA mutations cancer Carrier Proteins - chemistry Carrier Proteins - metabolism Cell Line, Tumor DNA Damage Down-Regulation - drug effects endogenous DNA lesions genome instability HECT-type ubiquitin ligases HEK293 Cells Humans Models, Biological Mutagens - toxicity Neoplasms - pathology PAR-targeted protein ubiquitylation PARP inhibitors personalized cancer therapy Poly (ADP-Ribose) Polymerase-1 - metabolism Poly Adenosine Diphosphate Ribose - metabolism Poly ADP Ribosylation - drug effects Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Proteasome Endopeptidase Complex - metabolism Protein Binding - drug effects Protein Domains Protein Stability - drug effects Proteolysis - drug effects replication stress Signal Transduction - drug effects synthetic lethality Ubiquitin-Protein Ligases - chemistry Ubiquitin-Protein Ligases - metabolism Ubiquitination - drug effects PAR-targeted protein ubiquitylation endogenous DNA lesions replication stress personalized cancer therapy genome instability HECT-type ubiquitin ligases BRCA mutations PARP inhibitors synthetic lethality cancer
ISSN:	2211-1247, 2211-1247
Online-Zugang:	Volltext
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