PXD014827

PXD014827 is an original dataset announced via ProteomeXchange.

Title	Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis
Description	Outcomes for metastatic bone sarcomas, Ewing sarcoma and osteosarcoma, are dismal and remain unchanged for decades. Oxidative stress attenuates melanoma metastasis, and melanoma cells must reduce oxidative stress to metastasize. To explore this in sarcomas, we screened libraries of approved compounds for agents sensitizing sarcoma cells to oxidative stress. This identified the class I HDAC inhibitor MS-275 as enhancing sensitivity to reactive oxygen species (ROS). Mechanistically, MS-275 inhibits YB-1 deacetylation, decreasing physical binding between YB-1 and the 5UTR of NFE2L2, thereby non-transcriptionally reducing translation and expression of the master antioxidant factor, NRF2, which reduces cellular ROS. Indeed, global acetylomics revealed that MS-275 promotes rapid acetylation of the YB-1 RNA binding protein at lysine-81, blocking RNA binding and translational activation of NFE2L2, encoding NRF2, as well as known YB-1 mRNA targets, HIF1A and the stress granule nucleator, G3BP1. MS-275 dramatically reduced sarcoma metastasis in vivo, but an MS-275-resistant YB-1 K81-to-alanine (K81A) mutant restored metastatic capacity and NRF2, HIF1α, and G3BP1 synthesis in MS-275 treated mice. These studies describe a novel function for MS-275 through enhanced YB-1 acetylation, thus inhibiting YB-1 translational control of key cytoprotective factors and its pro-metastatic activity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:58:39.229.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gian Luca Negri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-30 05:45:20	ID requested
1	2019-10-28 09:10:59	announced
⏵ 2	2024-10-22 04:58:39	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: YB-1, MS275, sarcoma, HDAC

Gregg B. Morin
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada.
contact email	gmorin@bcgsc.ca
lab head
Gian Luca Negri
contact affiliation	Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver V5Z 1L3, Canada.
contact email	gnegri@bcgsc.ca
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/2019/10/PXD014827

PRIDE project URI

• PRIDE
  1. PXD014827
     1. Label: PRIDE project
     2. Name: Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis