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 |
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| Authors: | Bizhan Romani Nima Shaykh Baygloo Mohammad Reza Aghasadeghi Elham Allahbakhshi |
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| 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 ;the ¶Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran 13169-43551, Iran |
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| 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. |
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| Keywords: | cell cycle E3 ubiquitin ligase human immunodeficiency virus (HIV) proteasome protein degradation ubiquitin HIV-1 Vpr MCM10 VprBP |
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