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PXD012540

PXD012540 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHDAC2 regulates site-specific acetylation of MDM2 and its ubiquitination signaling in tumor suppression
DescriptionHistone deacetylases (HDACs) are promising targets for cancer therapy, while their individual actions remain incompletely understood. Here, we identify a role for HDAC2 in regulation of MDM2 acetylation at previously uncharacterized lysines. Upon inactivation of HDAC2, this acetylation creates a structural signal in the lysine-rich domain of MDM2 to prevent the recognition and degradation of its downstream substrate, MCL-1 Ubiquitin Ligase E3 (MULE). This mechanism further reveals a therapeutic connection between the MULE ubiquitin ligase function and tumor suppression. Specifically, we show that HDAC inhibitor treatment promotes the accumulation of MULE, which diminishes the t(X;18) translocation-associated synovial sarcomagenesis by directly targeting the fusion product SS18-SSX for degradation. These results uncover a new HDAC2-dependent pathway that integrates reversible acetylation signaling to the anticancer ubiquitin response.
HostingRepositoryjPOST
AnnounceDate2020-03-22
AnnouncementXMLSubmission_2022-09-18_02:15:40.487.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKumiko Shiozawa
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListS-carboxymethyl-L-cysteine; N6-acetyl-L-lysine; L-methionine sulfoxide
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-01-28 19:29:06ID requested
12020-03-21 08:00:06announced
22021-02-04 17:17:28announced2021-02-04: Updated FTP location.
32022-09-18 02:15:40announced2022-09-18: Updated FTP location.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: FK228-treated endogeneous MDM2 IP
Contact List
Le Su
lab head
Kumiko Shiozawa
contact affiliationNational Cancer Centre
dataset submitter
Full Dataset Link List
jPOST dataset URI
Dataset FTP location
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