PXD065443

PXD065443 is an original dataset announced via ProteomeXchange.

Title	TMT expression proteomics of HAP1 cells acutely depleted of TADA1 (time course)
Description	The SAGA transcriptional co-activator complex regulates gene expression through histone acetylation at promoters, mediated by its histone acetyl transferase, KAT2A. While its structure and function have been extensively investigated, how the stability of individual subunits of SAGA, including KAT2A, is regulated, remains unclear. Here, using a fluorescence-based KAT2A stability reporter, we systematically dissect the molecular dependencies controlling KAT2A protein abundance. We identify the non-enzymatic SAGA CORE module subunits—TADA1, TAF5L, and TAF6L— as necessary for KAT2A stability, with loss of these subunits disrupting the integrity of SAGA, leading to non-chromatin-bound KAT2A that is degraded by the proteasome, consequently leading to reduced H3K9 acetylation. Proteomic profiling reveals progressive loss of CORE and HAT components upon acute disruption of the SAGA CORE, indicating that an intact CORE is required for the stability of numerous components of SAGA. Finally, a focused CRISPR screen of ubiquitin-proteasome system genes identifies the E3 ligase UBR5, a known regulator of orphan protein degradation, and the deubiquitinase OTUD5, as regulators of KAT2A degradation when the SAGA CORE is perturbed. Together, these findings reveal a dependency of KAT2A protein stability on SAGA CORE integrity and define an orphan quality control mechanism targeting unassembled KAT2A, revealing a potential vulnerability in SAGA-driven malignancies.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_04:20:37.105.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Batty
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-25 07:17:07	ID requested
⏵ 1	2026-03-16 04:20:37	announced

Dataset with its publication pending

submitter keyword: Human, SAGA, acute degradation,TMT expression proteomics, HAP1, TADA1

Davide Seruggia
contact affiliation	St Anna CCRI (Children's Cancer Research Institute), Vienna,Austria CeMM Center for Molecular Medicine, Vienna, Austria
contact email	davide.seruggia@ccri.at
lab head
Paul Batty
contact affiliation	CCRI (Children's Cancer Research Institute), Vienna
contact email	pauldanielbatty@gmail.com
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/2026/03/PXD065443

PRIDE project URI

• PRIDE
  1. PXD065443
     1. Label: PRIDE project
     2. Name: TMT expression proteomics of HAP1 cells acutely depleted of TADA1 (time course)