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

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

  • Virology. 2015 Mar;477:10-17. doi: 10.1016/j.virol.2014.12.040.
Ana Beatriz DePaula-Silva 1,  Patrick A Cassiday 1,  Jeffrey Chumley 1,  Alberto Bosque 1,  Carlos M R Monteiro-Filho 1,  Cathal S Mahon 2,  Kelsey R Cone 3,  Nevan Krogan 2,  Nels C Elde 3,  Vicente Planelles 4
Affiliations

Affiliations

  • 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: [email protected].
PMID: 25618414 DOI: 10.1016/j.virol.2014.12.040
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.

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