About: Phospho-Ser(784)-VCP Is Required for DNA Damage Response and Is Associated with Poor Prognosis of Chemotherapy-Treated Breast Cancer

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About: Phospho-Ser(784)-VCP Is Required for DNA Damage Response and Is Associated with Poor Prognosis of Chemotherapy-Treated Breast Cancer Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Phospho-Ser(784)-VCP Is Required for DNA Damage Response and Is Associated with Poor Prognosis of Chemotherapy-Treated Breast Cancer
Creator	Li, Shan Zhu, Jian Asleh, Karama Gao, Dongxia Held, Jason Leung, Samuel Nielsen, Torsten Rogers, Anna Shao Correspondence, Jieya Shao, Jieya Vij, Kiran Won, Jennifer You, Zhongsheng Zhu, Cuige
Source	Elsevier; Medline; PMC
abstract	Spatiotemporal protein reorganization at DNA damage sites induced by genotoxic chemotherapies is crucial for DNA damage response (DDR), which influences treatment response by directing cancer cell fate. This process is orchestrated by valosin-containing protein (VCP), an AAA+ ATPase that extracts polyubiquinated chromatin proteins and facilitates their turnover. However, because of the essential and pleiotropic effects of VCP in global proteostasis, it remains challenging practically to understand and target its DDR-specific functions. We describe a DNA-damage-induced phosphorylation event (Ser(784)), which selectively enhances chromatin-associated protein degradation mediated by VCP and is required for DNA repair, signaling, and cell survival. These functional effects of Ser(784) phosphorylation on DDR correlate with a decrease in VCP association with chromatin, cofactors NPL4/UFD1, and polyubiquitinated substrates. Clinically, high phospho-Ser(784)-VCP levels are significantly associated with poor outcome among chemotherapy-treated breast cancer patients. Thus, Ser(784) phosphorylation is a DDR-specific enhancer of VCP function and a potential predictive biomarker for chemotherapy treatments.
has issue date	2020-06-09(xsd:dateTime)
bibo:doi	10.1016/j.celrep.2020.107745
bibo:pmid	32521270
has license	no-cc
sha1sum (hex)	de44823945f6378ded214c5ed4f840b73f673a8b
schema:url	https://doi.org/10.1016/j.celrep.2020.107745
resource representing a document's title	Phospho-Ser(784)-VCP Is Required for DNA Damage Response and Is Associated with Poor Prognosis of Chemotherapy-Treated Breast Cancer
has PubMed Central identifier	PMC7282751
has PubMed identifier	32521270
schema:publication	Cell Rep
resource representing a document's body	covid:de44823945f6378ded214c5ed4f840b73f673a8b#body_text
is schema:about of	named entity 'cell' named entity 'phosphorylation' named entity 'VCP' named entity 'cancer patients' named entity 'PBS' named entity 'VCP' named entity 'NBS1' named entity 'protein' named entity 'S4D' named entity 'laser' named entity 'VCP' named entity 'VCP' named entity 'pSer' named entity 'PBS' named entity 'polyubiquitins' named entity 'SDS' named entity 'insoluble' named entity 'mass spectrometry' named entity 'Breast Cancer' named entity 'chemotherapies' named entity 'breast cancer' named entity 'protein' named entity 'pSer' named entity 'DNA damage response' named entity 'HER2' named entity 'subcloning' named entity 'antibody' named entity 'VCP' named entity 'puromycin' named entity 'inverted microscope' named entity 'pleiotropic effects' named entity 'chromatin' named entity 'clones' named entity 'antibody' named entity 'nucleoplasm' named entity 'phosphorylation' named entity 'VCP' named entity 'experimental evidence' named entity 'DNA-damage' named entity 'antibody' named entity 'gel electrophoresis' named entity 'antibody' named entity 'DMSO' named entity 'supernatants' named entity 'laser' named entity 'pSer' named entity 'antibody' named entity 'ATM' named entity 'phosphorylation' named entity 'motif' named entity 'conjugated' named entity 'DNA-damage' named entity 'antibody' named entity 'Molecular Devices' named entity 'pSer' named entity 'VCP' named entity 'vascular invasion' named entity 'chemotherapy' named entity 'VCP' named entity 'biomarker' named entity 'ATM' named entity 'chromatin' named entity 'VCP' named entity 'VCP' named entity 'chromatin' named entity 'genotoxic' named entity 'VCP' named entity 'phosphorylation'

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