PXD041220

PXD041220 is an original dataset announced via ProteomeXchange.

Title	c-Myc uses Cul4b to preserve genome stability and promote CD8+ T cell-mediated antiviral immune responses
Description	During infection, virus-specific CD8+ T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. We found that c-Myc utilizes the E3 ubiquitin ligase, Cul4b, to inextricably link CD8+ T cell expansion to DNA damage response pathways. Following activation, c-Myc increased levels of Cul4b and other members of the CRL4 complex. Despite having abundant c-Myc expression, Cul4b-deficient CD8+ T cells were unable to expand and clear virus. Cul4b-deficient CD8+ T cells accrued DNA damage and succumbed to proliferative catastrophe early after antigen encounter. Mechanistically, Cul4b ablation induced a protracted accumulation of p21 and Cyclin E2 resulting in replication stress. Our data show that, to support cell proliferation, c-Myc must employ Cul4b to maintain genome stability, thereby directly coupling these two interdependent pathways. These data clarify how CD8+ T cells use c-Myc and Cul4b to sustain their potential for extraordinary population expansion, longevity and antiviral responses.
HostingRepository	PRIDE
AnnounceDate	2023-08-29
AnnouncementXML	Submission_2023-08-29_03:49:52.358.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	HosseinFazelinia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-30 09:06:46	ID requested
⏵ 1	2023-08-29 03:49:52	announced

Dataset with its publication pending

submitter keyword: c-Myc, CD8+ T cells, Replication Stress, antiviral immune responses, E3 Ubiquitin ligases, Cul4b

Paula M. Olive,PhD
contact affiliation	University of Pennsylvania Children's Hospital of Philadelphia 816F ARC, 3615 Civic Center Blvd. Philadelphia, PA 19104 267-426-2839
contact email	paulao@pennmedicine.upenn.edu
lab head
HosseinFazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2023/08/PXD041220

PRIDE project URI

• PRIDE
  1. PXD041220
     1. Label: PRIDE project
     2. Name: c-Myc uses Cul4b to preserve genome stability and promote CD8+ T cell-mediated antiviral immune responses