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Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development.

Publication ,  Journal Article
McCall, CM; Miliani de Marval, PL; Chastain, PD; Jackson, SC; He, YJ; Kotake, Y; Cook, JG; Xiong, Y
Published in: Mol Cell Biol
September 2008

Damaged DNA binding protein 1, DDB1, bridges an estimated 90 or more WD40 repeats (DDB1-binding WD40, or DWD proteins) to the CUL4-ROC1 catalytic core to constitute a potentially large number of E3 ligase complexes. Among these DWD proteins is the human immunodeficiency virus type 1 (HIV-1) Vpr-binding protein VprBP, whose cellular function has yet to be characterized but has recently been found to mediate Vpr-induced G(2) cell cycle arrest. We demonstrate here that VprBP binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A, subunits of the COP9/signalsome, and DDA1. The steady-state level of VprBP remains constant during interphase and decreases during mitosis. VprBP binds to chromatin in a DDB1-independent and cell cycle-dependent manner, increasing from early S through G(2) before decreasing to undetectable levels in mitotic and G(1) cells. Silencing VprBP reduced the rate of DNA replication, blocked cells from progressing through the S phase, and inhibited proliferation. VprBP ablation in mice results in early embryonic lethality. Conditional deletion of the VprBP gene in mouse embryonic fibroblasts results in severely defective progression through S phase and subsequent apoptosis. Our studies identify a previously unknown function of VprBP in S-phase progression and suggest the possibility that HIV-1 Vpr may divert an ongoing chromosomal replication activity to facilitate viral replication.

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Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

September 2008

Volume

28

Issue

18

Start / End Page

5621 / 5633

Location

United States

Related Subject Headings

  • vpr Gene Products, Human Immunodeficiency Virus
  • Ubiquitin-Protein Ligases
  • RNA Interference
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
 

Citation

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ICMJE
MLA
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McCall, C. M., Miliani de Marval, P. L., Chastain, P. D., Jackson, S. C., He, Y. J., Kotake, Y., … Xiong, Y. (2008). Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol, 28(18), 5621–5633. https://doi.org/10.1128/MCB.00232-08
McCall, Chad M., Paula L. Miliani de Marval, Paul D. Chastain, Sarah C. Jackson, Yizhou J. He, Yojiro Kotake, Jeanette Gowen Cook, and Yue Xiong. “Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development.Mol Cell Biol 28, no. 18 (September 2008): 5621–33. https://doi.org/10.1128/MCB.00232-08.
McCall CM, Miliani de Marval PL, Chastain PD, Jackson SC, He YJ, Kotake Y, Cook JG, Xiong Y. Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol. 2008 Sep;28(18):5621–5633.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

September 2008

Volume

28

Issue

18

Start / End Page

5621 / 5633

Location

United States

Related Subject Headings

  • vpr Gene Products, Human Immunodeficiency Virus
  • Ubiquitin-Protein Ligases
  • RNA Interference
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans