PXD039886-1

PXD039886 is an original dataset announced via ProteomeXchange.

Title	Specific regulation of BACH1 by the hot-spot mutant p53R175H reveals a distinct gain of function mechanism
Description	p53 gain-of-function (GOF) mutations can lead to new tumor-driver activities, however it remains unknown whether different mutants act through similar mechanisms in vivo. In a proteomic screen, we identified BACH1 as a cellular factor that recognizes the p53 DNA binding domain depending on its mutation status. BACH1 specifically interacts with p53R175H but fails to bind wild type p53 or other hot-spot mutants. Interestingly, p53R175H acts as a repressor for BACH1-dependent ferroptosis by abrogating BACH1-mediated downregulation of SLC7A11 to promote tumor growth; conversely, p53R175H coactivates BACH1-dependent tumor metastasis by upregulating pro-metastatic gene expression. Mechanistically, p53R175H-mediated bidirectional regulation of BACH1 function is dependent on its ability to recruit the histone demethylase LSD2 to target promoters and differentially modulating transcription. Our study also provides evidence that each p53 mutant may act through a distinct GOF mechanism thus, have significant implications regarding how to eliminate the GOFs of specific p53 mutant for cancer therapy.
HostingRepository	PRIDE
AnnounceDate	2023-02-17
AnnouncementXML	Submission_2023-02-17_03:52:48.714.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD039886
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	huanli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-06 05:45:18	ID requested
⏵ 1	2023-02-17 03:52:49	announced
2	2023-02-24 01:50:34	announced	2023-02-24: Updated project metadata.

10.6019/PXD039886;

submitter keyword: p53R175H, GOF, LSD2, ferroptosis, BACH1, oxidative stress, tumor suppression,p53, metastasis

ZhenyiSu
contact affiliation	Columbia University Medical Center
contact email	zs2391@cumc.columbia.edu
lab head
huanli
contact affiliation	COLUMBIA UNIVERSITY MEDICAL CENTER
contact email	hl2977@cumc.columbia.edu
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/2023/02/PXD039886

PRIDE project URI

• PRIDE
  1. PXD039886
     1. Label: PRIDE project
     2. Name: Specific regulation of BACH1 by the hot-spot mutant p53R175H reveals a distinct gain of function mechanism