DOI: 10.1073/pnas.0702102104. Lentiviral Vpr usurps Cul4–DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle

Lentiviral Vpr usurps Cul4–DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle

10.1073/pnas.0702102104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The replication of viruses depends on the cell cycle status of the infected cells. Viruses have evolved functions that alleviate restrictions imposed on their replication by the host. Vpr, an accessory factor of primate lentiviruses, arrests cells at the DNA damage checkpoint in G 2 phase of the cell cycle, but the mechanism underlying this effect has remained elusive. Here we report that Vpr proteins of both the human (HIV-1) and the distantly related simian (SIVmac) immunodeficiency viruses specifically associate with a protein complex comprising subunits of E3 ubiquitin ligase assembled on Cullin-4 scaffold (Cul4–DDB1[VprBP]). We show that Vpr binding to Cul4–DDB1[VprBP] leads to increased neddylation and elevated intrinsic ubiquitin ligase activity of this E3. This effect is mediated through the VprBP subunit of the complex, which recently has been suggested to function as a substrate receptor for Cul4. We also demonstrate that VprBP regulates G 1 phase and is essential for the completion of DNA replication in S phase. Furthermore, the ability of Vpr to arrest cells in G 2 phase correlates with its ability to interact with Cul4–DDB1[VprBP] E3 complex. Our studies identify the Cul4–DDB1[VprBP] E3 ubiquitin ligase complex as the downstream effector of lentiviral Vpr for the induction of cell cycle arrest in G 2 phase and suggest that Vpr may use this complex to perturb other aspects of the cell cycle and DNA metabolism in infected cells.

Bibliography

Hrecka, K., Gierszewska, M., Srivastava, S., Kozaczkiewicz, L., Swanson, S. K., Florens, L., Washburn, M. P., & Skowronski, J. (2007). Lentiviral Vpr usurps Cul4âDDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proceedings of the National Academy of Sciences, 104(28), 11778â11783.

Authors 8

Kasia Hrecka (first)
Magdalena Gierszewska (additional)
Smita Srivastava (additional)
Lukasz Kozaczkiewicz (additional)
Selene K. Swanson (additional)
Laurence Florens (additional)
Michael P. Washburn (additional)
Jacek Skowronski (additional)

References 50 Referenced 198

Dates

Type	When
Created	18 years, 2 months ago (July 3, 2007, 8:54 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:26 p.m.)
Indexed	1 day, 19 hours ago (Sept. 3, 2025, 7:02 a.m.)
Issued	18 years, 1 month ago (July 10, 2007)
Published	18 years, 1 month ago (July 10, 2007)
Published Online	18 years, 1 month ago (July 10, 2007)
Published Print	18 years, 1 month ago (July 10, 2007)

Funders 0

None

BibTeX

@article{Hrecka_2007, title={Lentiviral Vpr usurps Cul4–DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0702102104}, DOI={10.1073/pnas.0702102104}, number={28}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Hrecka, Kasia and Gierszewska, Magdalena and Srivastava, Smita and Kozaczkiewicz, Lukasz and Swanson, Selene K. and Florens, Laurence and Washburn, Michael P. and Skowronski, Jacek}, year={2007}, month=jul, pages={11778–11783} }

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