PXD060955

PXD060955 is an original dataset announced via ProteomeXchange.

Title	A mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy
Description	Transcriptional coactivators of YAP/TAZ play key roles in cancers through transcriptional outputs. However, the mechanisms of their transactivation remain unclear, and effective and safe targeting solutions are lacking. Here, we discovered that YAP/ TAZ possess a hydrophobic transactivation domain (TAD). Knockout of TADs prevents tumor establishment due to growth defects and enhanced immune attack. TADs facilitate preinitiation complex (PIC) assembly by promoting TFIID recruitment in a TAF4-dependent manner and enhance RNA polymerase II (Pol II) elongation through MED15-dependent mediator complex recruitment. The bindings of TAD to the surface hydrophobic groove of MED15 induce its folding of the helix and hydrophobic interactions of TAD-MED15 boosts YAP-MED15 co-condensations thereby enhancing transcriptional hub formation and the expression of an oncogenic and immune suppressive transcriptional program. Synthesized small peptide TJ-M11 selectively disrupts the interactions of TADs with MED15 and TAF4, thereby suppressing tumor growth and sensitizing immunotherapy. This study indicates TADs of YAP/TAZ exhibit dual functions in PIC assembly and Pol II elongation, relying on hydrophobic interactions.
HostingRepository	PRIDE
AnnounceDate	2025-04-02
AnnouncementXML	Submission_2025-04-01_19:37:51.434.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Man Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-19 05:35:31	ID requested
⏵ 1	2025-04-01 19:37:51	announced

Dataset with its publication pending

submitter keyword: cancer therapy,YAP/TAZ,transactivation

Shuguo Sun
contact affiliation	Huazhong University of Science and Technology
contact email	shuguo@hust.edu.cn
lab head
Man Yu
contact affiliation	Huazhong University of Science and Techonology
contact email	yuman@hust.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060955
     1. Label: PRIDE project
     2. Name: A mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy