PXD016623

PXD016623 is an original dataset announced via ProteomeXchange.

Title	USP7 counteracts the activation of the mitotic program
Description	Chemical inhibitors of the deubiquitinase USP7 are currently being developed as anticancer agents, due to their capacity to activate P53. Regardless of this activity, USP7 inhibitors also generate DNA damage in a p53-independent manner. However, the mechanism of this genotoxicity remains unknown. Surprisingly, even if USP7 inhibitors stop DNA replication, this occurs concomitant to a premature activation of mitotic kinases such as CDK1, which impairs chromosome segregation and is toxic for mammalian cells. Mechanistically, we show that USP7 interacts with the phosphatase PP2A and regulates its function. Accordingly, USP7 or PP2A inhibition trigger similar changes on the phosphoproteome, with a particular bias towards mitotic targets. Supporting our model, the toxicity of USP7 inhibitors is alleviated by lowering CDK1 activity or by the chemical activation of PP2A. Our work sheds light into the mechanism of action of USP7 inhibitors and provides the first example of triggering premature mitotic entry through perturbation of ubiquitin signaling.
HostingRepository	PRIDE
AnnounceDate	2021-03-09
AnnouncementXML	Submission_2021-03-09_06:02:58.023.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eduardo Zarzuela
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-05 06:47:59	ID requested
⏵ 1	2021-03-09 06:02:58	announced

Dataset with its publication pending

submitter keyword: USP7

Javier Muñoz
contact affiliation	CNIO
contact email	jmunozpe@cnio.es
lab head
Eduardo Zarzuela
contact affiliation	Centro Nacional de Investigaciones Oncológicas
contact email	eduzarfer@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016623
     1. Label: PRIDE project
     2. Name: USP7 counteracts the activation of the mitotic program