PXD028683 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Class I HDAC overexpression promotes temozolomide resistance in glioma cells by regulating RAD18 expression |
Description | Overexpression of histone deacetylases (HDACs) in cancer commonly causes resistance to genotoxic based therapies. Here we report on the novel mechanism whereby overexpressed class I HDACs increase the resistance of glioblastoma cells to the SN1 methylating agent temozolomide (TMZ). The chemotherapeutic TMZ triggers the activation of the DNA damage response (DDR) in resistant glioma cells, leading to DNA lesion bypass and cellular survival. Mass spectrometry analysis revealed that the catalytic activity of class I HDACs stimulates the expression of the E3 ubiquitin ligase RAD18. Furthermore, the data show that RAD18 is part of the O6-methylguanine-induced DDR as TMZ induces the formation of RAD18 foci at sites of DNA damage. Downregulation of RAD18 by HDAC inhibition prevents glioma cells from activating the DDR upon TMZ exposure. Lastly, RAD18 or O6-methylguanine-DNA methyltransferase (MGMT) overexpression abolishes the sensitization effect of HDAC inhibition on TMZ-exposed glioma cells. Our study describes the mechanism whereby class I HDAC overexpression in glioma cells causes resistance to TMZ treatment. HDACs accomplish this by promoting the bypass of O6-methylguanine DNA lesions via enhancing RAD18 expression. It also provides a treatment option with HDAC inhibition to undermine this mechanism. |
HostingRepository | PRIDE |
AnnounceDate | 2022-04-01 |
AnnouncementXML | Submission_2022-04-01_03:45:51.979.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | F Butter |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-09-21 10:11:19 | ID requested | |
⏵ 1 | 2022-04-01 03:45:52 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: LC-MS/MS |
Contact List
Falk Butter |
contact affiliation | IMB, Ackermannweg 4, 55128 Mainz |
contact email | f.butter@imb-mainz.de |
lab head | |
F Butter |
contact affiliation | Quantitative Proteomics Institute of Molecular Biology (IMB) |
contact email | f.butter@imb-mainz.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD028683
- Label: PRIDE project
- Name: Class I HDAC overexpression promotes temozolomide resistance in glioma cells by regulating RAD18 expression