title: HIV-1 Vpr Protein Enhances Proteasomal Degradation of MCM10 DNA Replication Factor through the Cul4-DDB1[VprBP] E3 Ubiquitin Ligase to Induce G2/M Cell Cycle Arrest.
abstract: Human immunodeficiency virus type 1 Vpr is an accessory protein that induces G2/M cell cycle arrest. It is well documented that interaction of Vpr with the Cul4-DDB1[VprBP] E3 ubiquitin ligase is essential for the induction of G2/M arrest. In this study, we show that HIV-1 Vpr indirectly binds MCM10, a eukaryotic DNA replication factor, in a Vpr-binding protein (VprBP) (VprBP)-dependent manner. Binding of Vpr to MCM10 enhanced ubiquitination and proteasomal degradation of MCM10. G2/M-defective mutants of Vpr were not able to deplete MCM10, and we show that Vpr-induced depletion of MCM10 is related to the ability of Vpr to induce G2/M arrest. Our study demonstrates that MCM10 is the natural substrate of the Cul4-DDB1[VprBP] E3 ubiquitin ligase whose degradation is regulated by VprBP, but Vpr enhances the proteasomal degradation of MCM10 by interacting with VprBP.
authors.affiliation: From the Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441, the Cellular and Molecular Research Center (CMRC), Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz 61357-15794, and.
authors.forename: Bizhan
authors.initials: B
authors.lastname: Romani
authors.affiliation: From the Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441.
authors.forename: Nima
authors.initials: N
authors.lastname: Shaykh Baygloo
authors.affiliation: the Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran 13169-43551, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Aghasadeghi
authors.affiliation: the Cellular and Molecular Research Center (CMRC), Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz 61357-15794, and abakhshi_e@ajums.ac.ir.
authors.forename: Elham
authors.initials: E
authors.lastname: Allahbakhshi
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D044842:Cullin Proteins; C091435:DDB1 protein, human; D004268:DNA-Binding Proteins; C489613:MCM10 protein, human; D034741:RNA, Small Interfering; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D044767:Ubiquitin-Protein Ligases; C530533:DCAF1 protein, human; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex; D064110:Minichromosome Maintenance Proteins
keywords: E3 ubiquitin ligase; HIV-1 Vpr; MCM10; VprBP; cell cycle; human immunodeficiency virus (HIV); proteasome; protein degradation; ubiquitin