University of Natural Resources and Life Sciences, Vienna (BOKU) - Research portal

Logo BOKU Resarch Portal

Selected Publication:

Schröfelbauer, B; Hakata, Y; Landau, NR.
(2007): HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1.
Proc Natl Acad Sci U S A. 2007; 104(10):4130-4135 FullText FullText_BOKU

The Vpr accessory protein of HIV-1 induces a response similar to that of DNA damage. In cells expressing Vpr, the DNA damage sensing kinase, ATR, is activated, resulting in G(2) arrest and apoptosis. In addition, Vpr causes rapid degradation of the uracil-DNA glycosylases UNG2 and SMUG1. Although several cellular proteins have been reported to bind to Vpr, the mechanism by which Vpr mediates its biological effects is unknown. Using tandem affinity purification and mass spectrometry, we identified a predominant cellular protein that binds to Vpr as the damage-specific DNA-binding protein 1 (DDB1). In addition to its role in the repair of damaged DNA, DDB1 is a component of an E3 ubiquitin ligase that degrades numerous cellular substrates. Interestingly, DDB1 is targeted by specific regulatory proteins of other viruses, including simian virus 5 and hepatitis B. We show that the interaction with DDB1 mediates Vpr-induced apoptosis and UNG2/SMUG1 degradation and impairs the repair of UV-damaged DNA, which could account for G(2) arrest and apoptosis. The interaction with DDB1 may explain several of the diverse biological functions of Vpr and suggests potential roles for Vpr in HIV-1 replication.
Authors BOKU Wien:
Katinger Hermann
Find related publications in this database (using NML MeSH Indexing)
Apoptosis -
Cell Line -
DNA Damage -
DNA Glycosylases - metabolism
DNA Repair - metabolism
DNA-Binding Proteins - chemistry
Gene Products, vpr - physiology
Genes, vpr - genetics
HIV-1 - metabolism
Humans - metabolism
Protein Binding - metabolism
Time Factors - metabolism
Ubiquitin-Protein Ligases - metabolism
Ultraviolet Rays - metabolism
vpr Gene Products, Human Immunodeficiency Virus - metabolism

Find related publications in this database (Keywords)
proteasomal degradation
DNA repair
G(2) arrest

© BOKU Wien Imprint