Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme

Kosgodage, Uchini S., Uysal-Onganer, Pinar, MacLatchy, Amy, Kraev, Igor, Chatterton, Nicholas P., Nicholas, Anthony P., Inal, Jameel M. and Lange, Sigrun (2018) Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme. International journal of molecular sciences, 20 (1). ISSN 1422-0067

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Abstract / Description

Glioblastoma multiforme (GBM) is the most aggressive form of adult primary malignant brain tumour with poor prognosis. Extracellular vesicles (EVs) are a key-mediator through which GBM cells promote a pro-oncogenic microenvironment. Peptidylarginine deiminases (PADs), which catalyze the post-translational protein deimination of target proteins, are implicated in cancer, including via EV modulation. Pan-PAD inhibitor Cl-amidine affected EV release from GBM cells, and EV related microRNA cargo, with reduced pro-oncogenic microRNA21 and increased anti-oncogenic microRNA126, also in combinatory treatment with the chemotherapeutic agent temozolomide (TMZ). The GBM cell lines under study, LN18 and LN229, differed in PAD2, PAD3 and PAD4 isozyme expression. Various cytoskeletal, nuclear and mitochondrial proteins were identified to be deiminated in GBM, including prohibitin (PHB), a key protein in mitochondrial integrity and also involved in chemo-resistance. Post-translational deimination of PHB, and PHB protein levels, were reduced after 1 h treatment with pan-PAD inhibitor Cl-amidine in GBM cells. Histone H3 deimination was also reduced following Cl-amidine treatment. Multifaceted roles for PADs on EV-mediated pathways, as well as deimination of mitochondrial, nuclear and invadopodia related proteins, highlight PADs as novel targets for modulating GBM tumour communication.

Item Type: Article
Additional Information: ** From Europe PMC via Jisc Publications Router. ** Licence for this article: cc by (http://creativecommons.org/licenses/by/4.0/)
Uncontrolled Keywords: glioblastoma multiforme (GBM); peptidylarginine deiminase (PAD); extracellular vesicles (EVs); prohibitin (PHB); deiminated histone H3
Subjects: 500 Natural Sciences and Mathematics > 570 Life sciences; biology
Department: School of Human Sciences
SWORD Depositor: Pub Router
Depositing User: Pub Router
Date Deposited: 12 Mar 2019 15:55
Last Modified: 12 Mar 2019 15:55
URI: http://repository.londonmet.ac.uk/id/eprint/4577

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