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Virology. 2015 Mar;477:10-17. doi: 10.1016/j.virol.2014.12.040. Epub 2015 Jan 22.

Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr.

Author information

1
Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
2
Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
3
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
4
Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA. Electronic address: vicente.planelles@path.utah.edu.

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.

KEYWORDS:

Agm; DCAF1; G2 arrest; HIV-1; MLN4924; Mus81; SAMHD1; SIV; Ubiquitination; Vpr

PMID:
25618414
PMCID:
PMC4455942
DOI:
10.1016/j.virol.2014.12.040
[Indexed for MEDLINE]
Free PMC Article

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