Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme
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-transla...
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| Format: | Article |
| Language: | English |
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MDPI
2018
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| Online Access: | https://repository.londonmet.ac.uk/4577/1/article.pdf |
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| author | Kosgodage, Uchini S. Uysal-Onganer, Pinar MacLatchy, Amy Kraev, Igor Chatterton, Nicholas P. Nicholas, Anthony P. Inal, Jameel Lange, Sigrun |
| author_facet | Kosgodage, Uchini S. Uysal-Onganer, Pinar MacLatchy, Amy Kraev, Igor Chatterton, Nicholas P. Nicholas, Anthony P. Inal, Jameel Lange, Sigrun |
| author_sort | Kosgodage, Uchini S. |
| collection | LMU |
| 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. |
| first_indexed | 2024-07-09T03:57:34Z |
| format | Article |
| id | oai:repository.londonmet.ac.uk:4577 |
| institution | London Metropolitan University |
| language | English |
| last_indexed | 2024-07-09T03:57:34Z |
| publishDate | 2018 |
| publisher | MDPI |
| record_format | eprints |
| spelling | oai:repository.londonmet.ac.uk:45772020-03-18T11:21:33Z http://repository.londonmet.ac.uk/4577/ 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 Lange, Sigrun 570 Life sciences; biology 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. MDPI 2018-12-28 Article PeerReviewed text en cc_by_4 https://repository.londonmet.ac.uk/4577/1/article.pdf Kosgodage, Uchini S., Uysal-Onganer, Pinar, MacLatchy, Amy, Kraev, Igor, Chatterton, Nicholas P., Nicholas, Anthony P., Inal, Jameel 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 10.3390/ijms20010103 |
| spellingShingle | 570 Life sciences; biology Kosgodage, Uchini S. Uysal-Onganer, Pinar MacLatchy, Amy Kraev, Igor Chatterton, Nicholas P. Nicholas, Anthony P. Inal, Jameel Lange, Sigrun Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme |
| title | Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme |
| title_full | Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme |
| title_fullStr | Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme |
| title_full_unstemmed | Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme |
| title_short | Peptidylarginine deiminases post-translationally deiminate prohibitin and modulate extracellular vesicle release and microRNAs in glioblastoma multiforme |
| title_sort | peptidylarginine deiminases post translationally deiminate prohibitin and modulate extracellular vesicle release and micrornas in glioblastoma multiforme |
| topic | 570 Life sciences; biology |
| url | https://repository.londonmet.ac.uk/4577/1/article.pdf |
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