PXD052675-1

PXD052675 is an original dataset announced via ProteomeXchange.

Title	A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements
Description	Chromosomal instability (CIN) generates micronuclei, aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, exposing DNA to the cytoplasm and driving a pro-inflammatory, pro-metastatic environment. Here, we identify the autophagic receptor p62/SQSTM1 as a regulator of micronuclei. p62 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements, via exerting local spatial control on peri-micronuclear ESCRT-mediated repair activity. We demonstrate that proximity of micronuclei to mitochondria leads to oxidation-driven homo-oligomerization of p62, which triggers autophagic degradation of ESCRT components, thereby limiting their repair activity. Notably, we find that p62 levels correlate with increased chromothripsis across human cancer cell lines and with increased CIN in colorectal tumors. Thus, our study identifies p62 as a novel regulator of micronuclei and indicates that it may serve as a prognostic marker of tumors with high CIN.
HostingRepository	PRIDE
AnnounceDate	2024-09-02
AnnouncementXML	Submission_2024-09-02_00:20:38.630.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	alessandro cuomo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-29 06:42:24	ID requested
⏵ 1	2024-09-02 00:20:39	announced
2	2024-10-22 06:57:38	announced	2024-10-22: Updated project metadata.

10.1126/SCIENCE.ADJ8691;

submitter keyword: chromosome missegregation,micronuclei, p62

Stefano Santaguida
contact affiliation	Department of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy
contact email	stefano.santaguida@ieo.it
lab head
alessandro cuomo
contact affiliation	IEO
contact email	alessandro.cuomo@ieo.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD052675

PRIDE project URI

• PRIDE
  1. PXD052675
     1. Label: PRIDE project
     2. Name: A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements