Vpr, a small HIV auxiliary protein, hijacks the CUL4 ubiquitin ligase through DCAF1 to inactivate an unknown cellular target, leading to cell cycle arrest at the G(2) phase and cell death. Here we first sought to delineate the Vpr determinants involved in the binding to DCAF1 and to the target. On the one hand, the three α-helices of Vpr are necessary and sufficient for binding to DCAF1; on the other hand, nonlinear determinants in Vpr are required for binding to the target, as shown by using protein chimeras. We also underscore that a SRIG motif conserved in the C-terminal tail of Vpr proteins from HIV-1/SIVcpz and HIV-2/SIVsmm lineages is critical for G(2) arrest. Our results suggest that this motif may be predictive of the ability of Vpr proteins from other SIV lineages to mediate G(2) arrest. We took advantage of the characterization of a subset of G(2) arrest-defective, but DCAF1 binding-proficient mutants, to investigate whether Vpr interferes with cell viability independently of its ability to induce G(2) arrest. These mutants inhibited cell colony formation in HeLa cells and are cytotoxic in lymphocytes, unmasking a G(2) arrest-independent cytopathic effect of Vpr. Furthermore these mutants do not block cell cycle progression at the G(1) or S phases but trigger apoptosis through caspase 3. Disruption of DCAF1 binding restored efficiency of colony formation. However, DCAF1 binding per se is not sufficient to confer cytopathicity. These data support a model in which Vpr recruits DCAF1 to induce the degradation of two host proteins independently required for proper cell growth.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129155 | PMC |
http://dx.doi.org/10.1074/jbc.M111.220780 | DOI Listing |
J Prosthodont
January 2025
Department of Prosthodontics, Jordan University of Science & Technology, Irbid, Jordan.
Purpose: To investigate the feasibility and accuracy (trueness and precision) of facial scanning and virtual patient representation (VPR).
Materials And Methods: One participant was recruited and informed consent was obtained. VPR was performed 30 times with a custom fabricated intraoral scan body (ISB).
J Gen Virol
January 2025
Division of Infection and Immunity, UCL, London, WC1E 6BT, UK.
Human immunodeficiency virus (HIV) is an exemplar virus, still the most studied and best understood and a model for mechanisms of viral replication, immune evasion and pathogenesis. In this review, we consider the earliest stages of HIV infection from transport of the virion contents through the cytoplasm to integration of the viral genome into host chromatin. We present a holistic model for the virus-host interaction during this pivotal stage of infection.
View Article and Find Full Text PDFBiomolecules
December 2024
Department of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa Street 7, 30-387 Krakow, Poland.
Melanoma cells remain resistant to chemotherapy with cisplatin (CisPt) and doxorubicin (DOX). The abnormal expression of Receptor-Interacting Protein Kinase 4 (RIPK4) in certain melanomas contributes to tumour growth through the NFκB and Wnt/β-catenin signalling pathways, which are known to regulate chemoresistance and recurrence. Despite this, the role of RIPK4 in response to chemotherapeutics in melanoma has not been reported.
View Article and Find Full Text PDFEpigenetics Chromatin
January 2025
Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
Despite significant advances in HIV treatment, a definitive cure remains elusive. The first-in-human clinical trial of Excision BioTherapeutics' CRISPR-based HIV cure, EBT-101, demonstrated safety but failed to prevent viral rebound. These outcomes may result from the interplay of several factors.
View Article and Find Full Text PDFSoft Matter
January 2025
MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, P. R. China.
The incorporation of reversible sacrificial bonds is an important strategy for enhancing the mechanical properties of elastomers. However, the research on the viscoelasticity of vulcanized rubber with a reversible sacrificial bond network lags seriously. In this paper, the effects of metal coordination bonds on the mechanical properties of butadiene-styrene-vinylpyridine rubber vulcanizates (VPR) were systematically investigated.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!