Proteomics

Dataset Information

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EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma


ABSTRACT: 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).

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Stem Cell, Cell Culture

DISEASE(S): Brain Cancer

SUBMITTER: Torsten Mueller  

LAB HEAD: Marcel Kool

PROVIDER: PXD012318 | Pride | 2019-07-08

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20181009_FS1_TM_CX_1_RAW.raw Raw
20181009_FS1_TM_CX_2_RAW.raw Raw
20181009_FS1_TM_CX_3_20181012190243_RAW.raw Raw
20181009_FS1_TM_CX_E_RAW.raw Raw
20181009_FS1_TM_CX_IgG_1_RAW.raw Raw
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Publications

EZHIP/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma.

Hübner Jens-Martin JM   Müller Torsten T   Papageorgiou Dimitris N DN   Mauermann Monika M   Krijgsveld Jeroen J   Russell Robert B RB   Russell Robert B RB   Ellison David W DW   Pfister Stefan M SM   Pajtler Kristian W KW   Kool Marcel M  

Neuro-oncology 20190701 7


<h4>Background</h4>Posterior fossa A (PFA) ependymomas are one of 9 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 overexpression of chromosome X open reading frame 67 (CXorf67) as a hallmark of PFA ependymoma and showed that CXorf67 can interact with enhancer of zeste homolog 2 (EZH2), thereby inhibiti  ...[more]

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