PXD056446

PXD056446 is an original dataset announced via ProteomeXchange.

Title	BTG3-dependent VCP/p97 nuclear translocation is required for efficient repair of UV-induced DNA lesions
Description	Skin exposure to ultraviolet (UV) rays from sunlight results in the formation of mutagenic DNA photolesions that are repaired by the nucleotide excision repair (NER) machinery. The inefficient repair of photolesions can lead to stalled DNA replication and mispairing, thereby causing strand breaks and mutations. B-cell translocation gene 3 (BTG3) is expressed in the epidermis of the skin and is an antiproliferative gene that is upregulated in human keratinocytes after radiation injury. In this study, we found that BTG3 is required to promote the timely extraction of the lesion-binding protein XPC by the segregase VCP/p97, an essential step preceding the excision of photolesions. Mechanistically, we showed that BTG3-dependent CHK1 activation and phosphorylation of VCP/p97 at S775 are necessary for the nuclear translocation of VCP/p97 after UV irradiation. Thus, loss of BTG3 or inhibition of CHK1 results in cytoplasmic retention of VCP/p97 and accumulation of ubiquitinated XPC, leading to delayed removal of photolesions and inefficient NER, which was recapitulated in vivo in the skin of the Btg3 knockout mice showing increased photolesions and H2AX and elevated mutations after UV. Our findings revealed that by influencing the cellular localization of VCP/p97, BTG3 is critical for the proper execution of NER to protect cells from UV-induced damage and skin carcinogenesis.
HostingRepository	PRIDE
AnnounceDate	2025-07-14
AnnouncementXML	Submission_2025-07-13_16:08:18.607.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056446
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fu-An Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-02 05:15:29	ID requested
⏵ 1	2025-07-13 16:08:19	announced

10.1093/nar/gkaf626;

Acedera JD, Cheng YC, Li YJ, Hsueh HY, Shieh SY, BTG3-dependent VCP/p97 nuclear translocation is required for efficient repair of UV-induced DNA lesions. Nucleic Acids Res, 53(13):(2025) [pubmed]

10.6019/PXD056446;

submitter keyword: phosphorylation, LC-MS/MS

Sheau-Yann Shieh
contact affiliation	Institute of Biomedical Sciences, Academia Sinica
contact email	sy88@ibms.sinica.edu.tw
lab head
Fu-An Li
contact affiliation	Institute of Biomedical Sciences, Academia Sinica
contact email	falee@ibms.sinica.edu.tw
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/2025/07/PXD056446

PRIDE project URI

• PRIDE
  1. PXD056446
     1. Label: PRIDE project
     2. Name: BTG3-dependent VCP/p97 nuclear translocation is required for efficient repair of UV-induced DNA lesions