PXD068941

PXD068941 is an original dataset announced via ProteomeXchange.

Title	PARP1-mediated TEAD4 PARylation stabilizes YAP1-TEAD4 complex and promotes the malignancy and immune evasion of breast cancer
Description	YAP1 is participated in numerous biological processes including organ size control and tissue homeostasis. We previously reported that abnormal YAP1 activation accounted for the malignant characteristics of breast cancer, including stemness, metastasis and drug resistance. However, as a transcription coregulator, YAP1 was generally considered to be an undruggable target, which limits its further clinical application. Here, using co-immunoprecipitation and mass spectrometry analysis, we identified PARP1 as a novel regulator in the control of YAP1-TEAD4 transcriptional activity, breast cancer cell stemness, metastasis and immune evasion, which was independent on DNA damage response. Specifically, we found PARP1 directly interacted with YAP1-TEAD4 complex and enhanced their interactions through PARP1-mediated TEAD4 PARylation at a novel conserved R108K109 site. Moreover, PARP1-mediated YAP1-TEAD4 binding attenuated YAP1 interaction with CRL4DCAF12, and thus prevented YAP1 ubiquitination and degradation in cell nucleus. In addition, expression levels of PARP1 correlate with YAP1 and PD-L1 protein levels in breast cancer patient tissues and cells. Accordingly, simultaneous inhibition of PARP1 activity and blockade of PD-L1 enhanced CD8+/CD4+ cytolytic and tumor suppression functions in vivo. Overall, our findings not only reveal a new regulatory mechanism for PARP1-mediated YAP1-TEAD4 transcriptional activity, but also provide translational implications of targeting PARP1 for YAP1-TEAD4 complex-based anti-tumor therapy.
HostingRepository	iProX
AnnounceDate	2025-09-26
AnnouncementXML	Submission_2025-09-29_00:50:54.036.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peng Li
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-29 00:50:34	ID requested
⏵ 1	2025-09-29 00:50:54	announced

Dataset with its publication pending

submitter keyword: Breast cancer

YAP1-TEAD4

PARP1

PARylation

Immune evasion

Peng Li
contact affiliation	Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Shenzhen, 518107, Guangdong, China
contact email	lipeng56@mail.sysu.edu.cn
lab head
Peng Li
contact affiliation	Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Shenzhen, 518107, Guangdong, China
contact email	lipeng56@mail.sysu.edu.cn
dataset submitter

iProX dataset URI