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Title: Critical role of PP2A-B56 family protein degradation in HIV-1 Vif mediated G2 cell cycle arrest
Authors: Nagata, Kayoko
Shindo, Keisuke
Matsui, Yusuke
Shirakawa, Kotaro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-7469-1276 (unconfirmed)
Takaori-Kondo, Akifumi
Author's alias: 永田, 佳代子
新堂, 啓祐
白川, 康太郎
髙折, 晃史
Keywords: Virion infectivity factor
PP2A
HIV-1
Cell cycle arrest
Ubiquitination
Issue Date: 18-Jun-2020
Publisher: Elsevier B.V.
Journal title: Biochemical and Biophysical Research Communications
Volume: 527
Issue: 1
Start page: 257
End page: 263
Abstract: HIV-1 Vif forms an E3 ubiquitin ligase complex with host proteins to counteract host restrictive APOBEC3, and is also known to accumulate infected cells at the G2 phase to promote viral replication. However, the underlying mechanism of how Vif induces G2 arrest is not fully understood, and more specifically, direct target molecules of G2 arrest have not been identified. Here we show that degradation of B56 family proteins (PP2A-B56), one of the regulatory subunits of protein phosphatase 2A, is critical for the Vif-induced G2 arrest. NL4-3 Vif caused degradation of PP2A-B56, and complementation of PP2A-B56 overcome the Vif-induced arrest. Supportively, knockdown of PPP2R5D, one of PP2A-B56, by siRNA itself induced cell cycle arrest of non-infected cells. We also identified Vif residues I31 and R or K33 are determinants for inducing G2 arrest, and Vif variants that did not cause G2 arrest did not induce PPP2R5D degradation, although it maintain the ability to induce APOBEC3G degradation, showing strong correlation between Vif-induced arrest and PP2A-B56 degradation. In a sequence database of HIV-1 isolates, Vif strains harboring residues that presumably induce cell cycle arrest are approximately 43%, suggesting Vif-induced G2 arrest contributes to HIV-1 infection in vivo and spread. Our data help understand the mechanism of Vif-mediated arrest, and gain insights into general cell cycle regulation.
Rights: © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
The full-text file will be made open to the public on 18 June 2021 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/252377
DOI(Published Version): 10.1016/j.bbrc.2020.04.123
PubMed ID: 32446377
Appears in Collections:Journal Articles

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