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PXD060955

PXD060955 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy
DescriptionTranscriptional 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.
HostingRepositoryPRIDE
AnnounceDate2025-04-02
AnnouncementXMLSubmission_2025-04-01_19:37:51.434.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMan Yu
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListbiotinylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-02-19 05:35:31ID requested
12025-04-01 19:37:51announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: cancer therapy,YAP/TAZ,transactivation
Contact List
Shuguo Sun
contact affiliationHuazhong University of Science and Technology
contact emailshuguo@hust.edu.cn
lab head
Man Yu
contact affiliationHuazhong University of Science and Techonology
contact emailyuman@hust.edu.cn
dataset submitter
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Dataset FTP location
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