Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr
Abstract Vpr and Vpx are a group of highly related accessory proteins from primate lentiviruses. Despite the high degree of amino acid homology within this group, these proteins can be highly divergent in their functions. In this work, we constructed chimeric and mutant proteins between HIV-1 and SI...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2015-03, Vol.477, p.10-17 |
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| creator | DePaula-Silva, Ana Beatriz Cassiday, Patrick A Chumley, Jeffrey Bosque, Alberto Monteiro-Filho, Carlos M.R Mahon, Cathal S Cone, Kelsey R Krogan, Nevan Elde, Nels C Planelles, Vicente |
| description | Abstract Vpr and Vpx are a group of highly related accessory proteins from primate lentiviruses. Despite the high degree of amino acid homology within this group, these proteins can be highly divergent in their functions. In this work, we constructed chimeric and mutant proteins between HIV-1 and SIVagm Vpr in order to better understand the structure–function relationships. We tested these constructs for their abilities to induce G2 arrest in human cells and to degrade agmSAMHD1 and Mus81. We found that the C-terminus of HIV-1 Vpr, when transferred onto SIVagm Vpr, provides the latter with the de novo ability to induce G2 arrest in human cells. We confirmed that HIV-1 Vpr induces degradation of Mus81 although, surprisingly, degradation is independent and genetically separable from Vpr׳s ability to induce G2 arrest. |
| doi_str_mv | 10.1016/j.virol.2014.12.040 |
| format | Article |
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Despite the high degree of amino acid homology within this group, these proteins can be highly divergent in their functions. In this work, we constructed chimeric and mutant proteins between HIV-1 and SIVagm Vpr in order to better understand the structure–function relationships. We tested these constructs for their abilities to induce G2 arrest in human cells and to degrade agmSAMHD1 and Mus81. We found that the C-terminus of HIV-1 Vpr, when transferred onto SIVagm Vpr, provides the latter with the de novo ability to induce G2 arrest in human cells. We confirmed that HIV-1 Vpr induces degradation of Mus81 although, surprisingly, degradation is independent and genetically separable from Vpr׳s ability to induce G2 arrest.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2014.12.040</identifier><identifier>PMID: 25618414</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Agm ; Cell Cycle ; DCAF1 ; DNA-Binding Proteins - metabolism ; Endonucleases - metabolism ; G2 arrest ; Gene Products, vpr - genetics ; Gene Products, vpr - metabolism ; HeLa Cells ; HIV-1 ; HIV-1 - physiology ; Host-Pathogen Interactions ; Humans ; Infectious Disease ; MLN4924 ; Monomeric GTP-Binding Proteins - metabolism ; Mus81 ; Proteolysis ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; SAM Domain and HD Domain-Containing Protein 1 ; SAMHD1 ; Simian Immunodeficiency Virus - physiology ; SIV ; Ubiquitination ; Vpr</subject><ispartof>Virology (New York, N.Y.), 2015-03, Vol.477, p.10-17</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. 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Despite the high degree of amino acid homology within this group, these proteins can be highly divergent in their functions. In this work, we constructed chimeric and mutant proteins between HIV-1 and SIVagm Vpr in order to better understand the structure–function relationships. We tested these constructs for their abilities to induce G2 arrest in human cells and to degrade agmSAMHD1 and Mus81. We found that the C-terminus of HIV-1 Vpr, when transferred onto SIVagm Vpr, provides the latter with the de novo ability to induce G2 arrest in human cells. We confirmed that HIV-1 Vpr induces degradation of Mus81 although, surprisingly, degradation is independent and genetically separable from Vpr׳s ability to induce G2 arrest.</description><subject>Agm</subject><subject>Cell Cycle</subject><subject>DCAF1</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endonucleases - metabolism</subject><subject>G2 arrest</subject><subject>Gene Products, vpr - genetics</subject><subject>Gene Products, vpr - metabolism</subject><subject>HeLa Cells</subject><subject>HIV-1</subject><subject>HIV-1 - physiology</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Infectious Disease</subject><subject>MLN4924</subject><subject>Monomeric GTP-Binding Proteins - metabolism</subject><subject>Mus81</subject><subject>Proteolysis</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>SAM Domain and HD Domain-Containing Protein 1</subject><subject>SAMHD1</subject><subject>Simian Immunodeficiency Virus - physiology</subject><subject>SIV</subject><subject>Ubiquitination</subject><subject>Vpr</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1v1DAQtRCIbgu_AAn5yIEEj-NkkwNIVUu7K7XisLBXy7Eni5fEXuxkpf57nH4BJ2v83ryZN4-Qd8ByYFB92udHG3yfcwYiB54zwV6QBbCmylgh4CVZMCZ4VtWcn5DTGPcs1csle01OeFlBLUAsiLnEEcNgnXJjpJ0P1OAuKKNG6x31Hd2c364u4SO9nWINVDlDrTOTfoKvOVUhYBzTN12ttxnQ7SHc8zbrrdoNc_mGvOpUH_Ht43tGflx9_X6xym6-Xa8vzm8y5A0bs1ZVlSg6bBF1Y5q2gLpMQF0jN2zZaux0o1vdCGiWLdO6Ro0VM7xQLeetVsUZ-fKge5jaAY1GNwbVy0Owgwp30isr_0ec_Sl3_iiFKMtG8CTw4VEg-N9TciUHGzX2vXLopyghLcgZr2pI1Pf_znoe8nTaRPj8QMDk-GgxyKgtOo3GBtSjNN5KYHKOUu7lfZRyjlIClynKv2ae-3VvndWq_4V3GPd-Ci4dU4KMqUFu5rDnrEEwVtZNUfwBSv-mbg</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>DePaula-Silva, Ana Beatriz</creator><creator>Cassiday, Patrick A</creator><creator>Chumley, Jeffrey</creator><creator>Bosque, Alberto</creator><creator>Monteiro-Filho, Carlos M.R</creator><creator>Mahon, Cathal S</creator><creator>Cone, Kelsey R</creator><creator>Krogan, Nevan</creator><creator>Elde, Nels C</creator><creator>Planelles, Vicente</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150301</creationdate><title>Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr</title><author>DePaula-Silva, Ana Beatriz ; 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| issn | 0042-6822 1096-0341 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Agm Cell Cycle DCAF1 DNA-Binding Proteins - metabolism Endonucleases - metabolism G2 arrest Gene Products, vpr - genetics Gene Products, vpr - metabolism HeLa Cells HIV-1 HIV-1 - physiology Host-Pathogen Interactions Humans Infectious Disease MLN4924 Monomeric GTP-Binding Proteins - metabolism Mus81 Proteolysis Recombinant Proteins - genetics Recombinant Proteins - metabolism SAM Domain and HD Domain-Containing Protein 1 SAMHD1 Simian Immunodeficiency Virus - physiology SIV Ubiquitination Vpr |
| title | Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr |
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