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HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity
HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (CycK) and...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385645/ https://www.ncbi.nlm.nih.gov/pubmed/34380030 http://dx.doi.org/10.1016/j.celrep.2021.109514 |
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author | Chai, Qingqing Li, Sunan Collins, Morgan K. Li, Rongrong Ahmad, Iqbal Johnson, Silas F. Frabutt, Dylan A. Yang, Zhichang Shen, Xiaojing Sun, Liangliang Hu, Jian Hultquist, Judd F. Peterlin, B. Matija Zheng, Yong-Hui |
author_facet | Chai, Qingqing Li, Sunan Collins, Morgan K. Li, Rongrong Ahmad, Iqbal Johnson, Silas F. Frabutt, Dylan A. Yang, Zhichang Shen, Xiaojing Sun, Liangliang Hu, Jian Hultquist, Judd F. Peterlin, B. Matija Zheng, Yong-Hui |
author_sort | Chai, Qingqing |
collection | PubMed |
description | HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (CycK) and cyclin-dependent kinase 13 (CDK13) as a Nef-associated kinase complex. CycK/CDK13 phosphorylates the serine at position 360 (S360) in SERINC5, which is required for Nef downregulation of SERINC5 from the cell surface and its counteractivity of the SERINC5 antiviral activity. To understand the role of S360 phosphorylation, we generate chimeric proteins between CD8 and SERINC5 to study their response to Nef. Nef not only downregulates but, importantly, also binds to this chimera in an S360-dependent manner. Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery. |
format | Online Article Text |
id | pubmed-8385645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-83856452021-08-25 HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity Chai, Qingqing Li, Sunan Collins, Morgan K. Li, Rongrong Ahmad, Iqbal Johnson, Silas F. Frabutt, Dylan A. Yang, Zhichang Shen, Xiaojing Sun, Liangliang Hu, Jian Hultquist, Judd F. Peterlin, B. Matija Zheng, Yong-Hui Cell Rep Article HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (CycK) and cyclin-dependent kinase 13 (CDK13) as a Nef-associated kinase complex. CycK/CDK13 phosphorylates the serine at position 360 (S360) in SERINC5, which is required for Nef downregulation of SERINC5 from the cell surface and its counteractivity of the SERINC5 antiviral activity. To understand the role of S360 phosphorylation, we generate chimeric proteins between CD8 and SERINC5 to study their response to Nef. Nef not only downregulates but, importantly, also binds to this chimera in an S360-dependent manner. Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery. 2021-08-10 /pmc/articles/PMC8385645/ /pubmed/34380030 http://dx.doi.org/10.1016/j.celrep.2021.109514 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Chai, Qingqing Li, Sunan Collins, Morgan K. Li, Rongrong Ahmad, Iqbal Johnson, Silas F. Frabutt, Dylan A. Yang, Zhichang Shen, Xiaojing Sun, Liangliang Hu, Jian Hultquist, Judd F. Peterlin, B. Matija Zheng, Yong-Hui HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
title | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
title_full | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
title_fullStr | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
title_full_unstemmed | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
title_short | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
title_sort | hiv-1 nef interacts with the cyclin k/cdk13 complex to antagonize serinc5 for optimal viral infectivity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385645/ https://www.ncbi.nlm.nih.gov/pubmed/34380030 http://dx.doi.org/10.1016/j.celrep.2021.109514 |
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