PXD029652

PXD029652 is an original dataset announced via ProteomeXchange.

Title	EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation
Description	Efforts to therapeutically target EZH2 have generally focused on inhibition of its methyltransferase activity, although it remains less clear whether this is the central mechanism whereby EZH2 promotes cancer. We demonstrate that EZH2 directly interacts with both MYC family oncoproteins, MYC and MYCN, and promotes their stabilization in a methyltransferase-independent manner. By competing against the SCFFBW7 ubiquitin ligase to bind MYC and MYCN, EZH2 counteracted FBW7-mediated MYC(N) polyubiquitination and proteasomal degradation. Depletion, but not enzymatic inhibition, of EZH2 induced robust MYC(N) degradation and inhibited tumor cell growth in MYC(N) driven neuroblastoma and small cell lung cancer. These findings unveil the MYC family proteins as global EZH2 oncogenic effectors and EZH2 pharmacologic degraders as potential MYC(N) targeted cancer therapeutics, pointing out that MYC(N) driven cancers may develop inherent resistance to the canonical EZH2 enzymatic inhibitors currently in clinical development.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_03:16:58.081.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	zemin song
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-10 07:53:48	ID requested
⏵ 1	2022-02-17 03:16:58	announced

Wang L, Chen C, Song Z, Wang H, Ye M, Wang D, Kang W, Liu H, Qing G, EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation. Nat Commun, 13(1):12(2022) [pubmed]

submitter keyword: MYC, MYCN, EZH2, AP-MS

Guoliang Qing
contact affiliation	Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, China
contact email	qingguoliang@whu.edu.cn
lab head
zemin song
contact affiliation	school of basic medicine, wuhan university, Wuhan 430071, China
contact email	songzm@whu.edu.cn
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/2022/02/PXD029652

PRIDE project URI

• PRIDE
  1. PXD029652
     1. Label: PRIDE project
     2. Name: EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation