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Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity
BACKGROUND: Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates arginine residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and interfering with the functions of several HIV-1 proteins, i....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750301/ https://www.ncbi.nlm.nih.gov/pubmed/23866860 http://dx.doi.org/10.1186/1742-4690-10-73 |
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author | Singhroy, Diane N Mesplède, Thibault Sabbah, Arielle Quashie, Peter K Falgueyret, Jean-Pierre Wainberg, Mark A |
author_facet | Singhroy, Diane N Mesplède, Thibault Sabbah, Arielle Quashie, Peter K Falgueyret, Jean-Pierre Wainberg, Mark A |
author_sort | Singhroy, Diane N |
collection | PubMed |
description | BACKGROUND: Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates arginine residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and interfering with the functions of several HIV-1 proteins, i.e. Tat, Rev and nucleocapsid (NC). PRMT6 also displays automethylation capacity but the role of this post-translational modification in its antiretroviral activity remains unknown. RESULTS: Here we report the identification by liquid chromatography-mass spectrometry of R35 within PRMT6 as the target residue for automethylation and have confirmed this by site-directed mutagenesis and in vitro and in vivo methylation assays. We further show that automethylation at position 35 greatly affects PRMT6 stability and is indispensable for its antiretroviral activity, as demonstrated in HIV-1 single-cycle TZM-bl infectivity assays. CONCLUSION: These results show that PRMT6 automethylation plays a role in the stability of this protein and that this event is indispensible for its anti-HIV-1 activity. |
format | Online Article Text |
id | pubmed-3750301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37503012013-08-24 Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity Singhroy, Diane N Mesplède, Thibault Sabbah, Arielle Quashie, Peter K Falgueyret, Jean-Pierre Wainberg, Mark A Retrovirology Research BACKGROUND: Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates arginine residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and interfering with the functions of several HIV-1 proteins, i.e. Tat, Rev and nucleocapsid (NC). PRMT6 also displays automethylation capacity but the role of this post-translational modification in its antiretroviral activity remains unknown. RESULTS: Here we report the identification by liquid chromatography-mass spectrometry of R35 within PRMT6 as the target residue for automethylation and have confirmed this by site-directed mutagenesis and in vitro and in vivo methylation assays. We further show that automethylation at position 35 greatly affects PRMT6 stability and is indispensable for its antiretroviral activity, as demonstrated in HIV-1 single-cycle TZM-bl infectivity assays. CONCLUSION: These results show that PRMT6 automethylation plays a role in the stability of this protein and that this event is indispensible for its anti-HIV-1 activity. BioMed Central 2013-07-17 /pmc/articles/PMC3750301/ /pubmed/23866860 http://dx.doi.org/10.1186/1742-4690-10-73 Text en Copyright © 2013 Singhroy et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Singhroy, Diane N Mesplède, Thibault Sabbah, Arielle Quashie, Peter K Falgueyret, Jean-Pierre Wainberg, Mark A Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity |
title | Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity |
title_full | Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity |
title_fullStr | Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity |
title_full_unstemmed | Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity |
title_short | Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity |
title_sort | automethylation of protein arginine methyltransferase 6 (prmt6) regulates its stability and its anti-hiv-1 activity |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750301/ https://www.ncbi.nlm.nih.gov/pubmed/23866860 http://dx.doi.org/10.1186/1742-4690-10-73 |
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