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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
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.
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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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