PXD012318-1

PXD012318 is an original dataset announced via ProteomeXchange.

Title	EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma
Description	Posterior fossa A (PFA) ependymomas comprise one out of nine molecular groups of ependymoma. PFA tumors are mainly diagnosed in infants and young children, show a poor prognosis and are characterized by a lack of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark. Recently, we reported CXorf67 overexpression as hallmark of PFA ependymoma and showed that CXorf67 can interact with EZH2 thereby inhibiting polycomb repressive complex 2 (PRC2). Here, we report that the inhibitory mechanism of this interaction is similar as in diffuse midline gliomas harboring H3K27M mutations. A small, highly conserved peptide sequence located in the C-terminal region of CXorf67 mimics the H3K27M peptide and binds to the SET domain of EZH2. This interaction blocks EZH2 methyltransferase activity and causes H3K27 hypomethylation, an oncogenic mechanism that may be exploited for targeted therapy in PFA ependymoma. Based on its function, we have renamed CXorf67 into EZH2 Inhibitory Protein (EZHIP).
HostingRepository	PRIDE
AnnounceDate	2019-07-08
AnnouncementXML	Submission_2019-07-08_01:15:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Torsten Mueller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-14 05:14:42	ID requested
⏵ 1	2019-07-08 01:15:08	announced
2	2024-10-22 04:52:21	announced	2024-10-22: Updated project metadata.

H, ü, bner JM, M, ü, ller T, Papageorgiou DN, Mauermann M, Krijgsveld J, Russell RB, Ellison DW, Pfister SM, Pajtler KW, Kool M, EZHIP/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma. Neuro Oncol, 21(7):878-889(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: Ependymoma, PRC2, EZHIP, CXorf67

Marcel Kool
contact affiliation	Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany & Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ), 69120 Heidelberg, Germany
contact email	m.kool@kitz-heidelberg.de
lab head
Torsten Mueller
contact affiliation	DKFZ
contact email	torsten.mueller84@googlemail.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/2019/07/PXD012318

PRIDE project URI

• PRIDE
  1. PXD012318
     1. Label: PRIDE project
     2. Name: EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma