DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest

Lindi Tan, Elana Ehrlich, Xiao Fang Yu

Research output: Contribution to journalArticle

Abstract

Vpr-mediated induction of G2 cell cycle arrest has been postulated to be important for human immunodeficiency virus type 1 (HIV-1) replication, but the precise role of Vpr in this cell cycle arrest is unclear. In the present study, we have shown that HIV-1 Vpr interacts with damaged DNA binding protein 1 (DDB1) but not its partner DDB2. The interaction of Vpr with DDB1 was inhibited when DCAF1 (VprBP) expression was reduced by short interfering RNA (siRNA) treatment. The Vpr mutant (Q65R) that was defective for DCAF1 interaction also had a defect in DDB1 binding. However, Vpr binding to DDB1 was not sufficient to induce G2 arrest. A reduction in DDB1 or DDB2 expression in the absence of Vpr also did not induce G2 arrest. On the other hand, Vpr-induced G2 arrest was impaired when the intracellular level of DDB1 or Cullin 4A was reduced by siRNA treatment. Furthermore, Vpr-induced G2 arrest was largely abolished by a proteasome inhibitor. These data suggest that Vpr assembles with DDB1 through interaction with DCAF1 to form an E3 ubiquitin ligase that targets cellular substrates for proteasome-mediated degradation and G2 arrest.

Original languageEnglish (US)
Pages (from-to)10822-10830
Number of pages9
JournalJournal of Virology
Volume81
Issue number19
DOIs
StatePublished - Oct 2007

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DNA-binding proteins
DNA-Binding Proteins
Human immunodeficiency virus 1
HIV-1
proteasome endopeptidase complex
small interfering RNA
Small Interfering RNA
G2 Phase Cell Cycle Checkpoints
ubiquitin-protein ligase
Proteasome Inhibitors
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Virus Replication
Cell Cycle Checkpoints
Protein Binding
mutants
degradation

ASJC Scopus subject areas

  • Immunology

Cite this

DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. / Tan, Lindi; Ehrlich, Elana; Yu, Xiao Fang.

In: Journal of Virology, Vol. 81, No. 19, 10.2007, p. 10822-10830.

Research output: Contribution to journalArticle

Tan, Lindi ; Ehrlich, Elana ; Yu, Xiao Fang. / DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. In: Journal of Virology. 2007 ; Vol. 81, No. 19. pp. 10822-10830.
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