title: 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 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.
authors.affiliation: 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.
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: DePaula-Silva
authors.affiliation: 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.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Cassiday
authors.affiliation: 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.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chumley
authors.affiliation: 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.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosque
authors.affiliation: 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.
authors.forename: Carlos M R
authors.initials: CMR
authors.lastname: Monteiro-Filho
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Cathal S
authors.initials: CS
authors.lastname: Mahon
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Kelsey R
authors.initials: KR
authors.lastname: Cone
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Nevan
authors.initials: N
authors.lastname: Krogan
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Nels C
authors.initials: NC
authors.lastname: Elde
authors.affiliation: 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.
authors.forename: Vicente
authors.initials: V
authors.lastname: Planelles
mesh_terms: D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D059748:Proteolysis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000076106:SAM Domain and HD Domain-Containing Protein 1; D015302:Simian Immunodeficiency Virus / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D016336:Gene Products, vpr; D011994:Recombinant Proteins; D004720:Endonucleases; C498772:MUS81 protein, human; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: Agm; DCAF1; G2 arrest; HIV-1; MLN4924; Mus81; SAMHD1; SIV; Ubiquitination; Vpr