P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity
The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize...
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| Veröffentlicht in: | PLoS pathogens 2021-06, Vol.17 (6), p.e1009616-e1009616 |
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| creator | Zhang, Linliang Zhou, Shixiong Chen, Majuan Yan, Jie Yang, Yi Wu, Linjuan Jin, Dongning Yin, Lei Chen, Mingzhou Qin, Yali |
| description | The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress. |
| doi_str_mv | 10.1371/journal.ppat.1009616 |
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Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1009616</identifier><identifier>PMID: 34111220</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Acetylation ; Acetyltransferase ; Antibodies ; Biology and Life Sciences ; Budding ; Cell lines ; Ebola virus ; Ebolavirus ; Egress ; Genetic aspects ; Hypotheses ; Life cycles ; Ligases ; Mass spectrometry ; Matrix protein ; Medicine and Health Sciences ; Phosphorylation ; Physical Sciences ; Physiological aspects ; Physiological effects ; Plasmids ; Post-translation ; Post-translational modification ; Proteins ; Regulatory mechanisms (biology) ; Research and Analysis Methods ; Scientific imaging ; Transcriptional coactivators ; Ubiquitin-proteasome system ; Ubiquitin-protein ligase ; Ubiquitination ; Viral infections ; Virus research ; Viruses ; VP40 protein</subject><ispartof>PLoS pathogens, 2021-06, Vol.17 (6), p.e1009616-e1009616</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Zhang et al 2021 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c638t-708051696511823237b1a93044cfa2efa5b443140db75535062fdc731e7c6a5f3</citedby><cites>FETCH-LOGICAL-c638t-708051696511823237b1a93044cfa2efa5b443140db75535062fdc731e7c6a5f3</cites><orcidid>0000-0001-5203-2766 ; 0000-0001-5308-6897</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191996/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191996/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids></links><search><contributor>Hartman, Amy L.</contributor><creatorcontrib>Zhang, Linliang</creatorcontrib><creatorcontrib>Zhou, Shixiong</creatorcontrib><creatorcontrib>Chen, Majuan</creatorcontrib><creatorcontrib>Yan, Jie</creatorcontrib><creatorcontrib>Yang, Yi</creatorcontrib><creatorcontrib>Wu, Linjuan</creatorcontrib><creatorcontrib>Jin, Dongning</creatorcontrib><creatorcontrib>Yin, Lei</creatorcontrib><creatorcontrib>Chen, Mingzhou</creatorcontrib><creatorcontrib>Qin, Yali</creatorcontrib><title>P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity</title><title>PLoS pathogens</title><description>The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.</description><subject>Acetylation</subject><subject>Acetyltransferase</subject><subject>Antibodies</subject><subject>Biology and Life Sciences</subject><subject>Budding</subject><subject>Cell lines</subject><subject>Ebola virus</subject><subject>Ebolavirus</subject><subject>Egress</subject><subject>Genetic aspects</subject><subject>Hypotheses</subject><subject>Life cycles</subject><subject>Ligases</subject><subject>Mass spectrometry</subject><subject>Matrix protein</subject><subject>Medicine and Health Sciences</subject><subject>Phosphorylation</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Physiological effects</subject><subject>Plasmids</subject><subject>Post-translation</subject><subject>Post-translational 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drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity</title><author>Zhang, Linliang ; Zhou, Shixiong ; Chen, Majuan ; Yan, Jie ; Yang, Yi ; Wu, Linjuan ; Jin, Dongning ; Yin, Lei ; Chen, Mingzhou ; Qin, Yali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c638t-708051696511823237b1a93044cfa2efa5b443140db75535062fdc731e7c6a5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetylation</topic><topic>Acetyltransferase</topic><topic>Antibodies</topic><topic>Biology and Life Sciences</topic><topic>Budding</topic><topic>Cell lines</topic><topic>Ebola virus</topic><topic>Ebolavirus</topic><topic>Egress</topic><topic>Genetic aspects</topic><topic>Hypotheses</topic><topic>Life cycles</topic><topic>Ligases</topic><topic>Mass spectrometry</topic><topic>Matrix protein</topic><topic>Medicine and Health Sciences</topic><topic>Phosphorylation</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Physiological effects</topic><topic>Plasmids</topic><topic>Post-translation</topic><topic>Post-translational modification</topic><topic>Proteins</topic><topic>Regulatory mechanisms (biology)</topic><topic>Research and Analysis Methods</topic><topic>Scientific imaging</topic><topic>Transcriptional coactivators</topic><topic>Ubiquitin-proteasome system</topic><topic>Ubiquitin-protein ligase</topic><topic>Ubiquitination</topic><topic>Viral infections</topic><topic>Virus research</topic><topic>Viruses</topic><topic>VP40 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Linliang</creatorcontrib><creatorcontrib>Zhou, Shixiong</creatorcontrib><creatorcontrib>Chen, Majuan</creatorcontrib><creatorcontrib>Yan, Jie</creatorcontrib><creatorcontrib>Yang, Yi</creatorcontrib><creatorcontrib>Wu, Linjuan</creatorcontrib><creatorcontrib>Jin, Dongning</creatorcontrib><creatorcontrib>Yin, 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pathogens</jtitle><date>2021-06-10</date><risdate>2021</risdate><volume>17</volume><issue>6</issue><spage>e1009616</spage><epage>e1009616</epage><pages>e1009616-e1009616</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34111220</pmid><doi>10.1371/journal.ppat.1009616</doi><orcidid>https://orcid.org/0000-0001-5203-2766</orcidid><orcidid>https://orcid.org/0000-0001-5308-6897</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylation Acetyltransferase Antibodies Biology and Life Sciences Budding Cell lines Ebola virus Ebolavirus Egress Genetic aspects Hypotheses Life cycles Ligases Mass spectrometry Matrix protein Medicine and Health Sciences Phosphorylation Physical Sciences Physiological aspects Physiological effects Plasmids Post-translation Post-translational modification Proteins Regulatory mechanisms (biology) Research and Analysis Methods Scientific imaging Transcriptional coactivators Ubiquitin-proteasome system Ubiquitin-protein ligase Ubiquitination Viral infections Virus research Viruses VP40 protein |
| title | P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity |
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