| 词条 | Vpr |
| 释义 |
| Symbol = VPR | Name = VPR | image = PDB 1fi0 EBI.jpg | width = | caption = solution structure of hiv-1 vpr (13-33) peptide in micells | Pfam = PF00522 | Pfam_clan = | InterPro = IPR000012 | SMART = | PROSITE = | MEROPS = | SCOP = 1dsk | TCDB = 1.A.42 | OPM family = | OPM protein = | CAZy = | CDD = }}Vpr is a Human immunodeficiency virus gene and protein product.[1][2] Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for virus replication in non-dividing cells such as macrophages. Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.[3][4] Vpr is also immunosuppressive due to its ability to sequester a proinflammatory transcriptional activator in the cytoplasm. HIV-2 contains both a Vpr protein and a related (by sequence homology) Vpx protein (Viral Protein X). Two functions of Vpr in HIV-1 are split between Vpr and Vpx in HIV-2, with the HIV-2 Vpr protein inducing cell cycle arrest and the Vpx protein required for nuclear import. Vpr-Binding ProteinVpr-binding protein (VprBP) is a 1,507-amino-acid human protein that contains conserved domains, including YXXY repeats, the Lis homology motif, and WD40 repeats.[5] VprBP acts as a substrate-recognition unit when associated with DNA damage-binding protein 1 (DDB1) as part of a CUL4–DDB1 E3 ubiquitin ligase complex.[5] When bound to Vpr, VprBP allows Vpr to modulate the catalytic activity of the CUL4–DDB1 complex, inducing G2 cell cycle arrest in infected cells.[5] VprBP also regulates p53-induced transcription and apoptotic pathways. p53 is an important tumor suppressor which induces either cell cycle arrest or apoptosis in response to DNA damage.[5] In-vitro studies of VprThe lack of an in vitro cell culture system that demonstrated a deficit in replication upon infection with viruses in the absence of Vpr has led to some mystery in the function of Vpr. Recently, there has been experiments on monocyte-derived dendritic cells (MDDCs) using a novel in-vitro infection system. These infected human dendritic cells showed a slower rate of replication when deprived of the Vpr protein in HIV-1 cells. This replication difference occurred in a single round of infection. This was shown to be due to decreased transcriptional output from the integrated HIV viral genome. Using mutational analysis (biochemical identification of mutational changes in a nucleotide sequence), prevention of cell cycle progression into mitosis was shown to be required for LTR-mediated viral expression. These findings suggest that the evolutionarily secured G2 cell cycle arrest function of Vpr (Viral Protein R) is essential for HIV-1 replication. Furthermore, this innovative in-vitro culture system will allow researchers to address mechanisms underlying Vpr-mediated enhancement of HIV-1 replication. [6]References1. ^{{MeshName|Vpr+Gene+Products,+Human+Immunodeficiency+Virus}} {{Viral proteins}}2. ^{{MeshName|Genes,+Vpr}} 3. ^{{cite journal | vauthors = Bukrinsky M, Adzhubei A | title = Viral protein R of HIV-1 | journal = Reviews in Medical Virology | volume = 9 | issue = 1 | pages = 39–49 | year = 1999 | pmid = 10371671 | doi = 10.1002/(SICI)1099-1654(199901/03)9:1<39::AID-RMV235>3.0.CO;2-3 }} 4. ^{{cite journal | vauthors = Muthumani K, Choo AY, Zong WX, Madesh M, Hwang DS, Premkumar A, Thieu KP, Emmanuel J, Kumar S, Thompson CB, Weiner DB | title = The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1 | journal = Nature Cell Biology | volume = 8 | issue = 2 | pages = 170–9 | date = February 2006 | pmid = 16429131 | pmc = 3142937 | doi = 10.1038/ncb1352 }} 5. ^1 2 3 {{cite journal | vauthors = Kim K, Heo K, Choi J, Jackson S, Kim H, Xiong Y, An W | title = Vpr-binding protein antagonizes p53-mediated transcription via direct interaction with H3 tail | journal = Molecular and Cellular Biology | volume = 32 | issue = 4 | pages = 783–96 | date = February 2012 | pmid = 22184063 | pmc = 3272969 | doi = 10.1128/MCB.06037-11 }} 6. ^{{cite journal | vauthors = Miller CM, Akiyama H, Agosto LM, Emery A, Ettinger CR, Swanstrom RI, Henderson AJ, Gummuluru S | title = Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of Dendritic Cells | journal = Journal of Virology | volume = 91 | issue = 13 | date = July 2017 | pmid = 28424288 | pmc = 5469257 | doi = 10.1128/JVI.00051-17 }} 2 : Viral proteins|HIV/AIDS |
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