Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities.
The UV-damaged DNA-binding activity protein (UV-DDB) consists of two subunits, DDB1 and DDB2, and functions in DNA repair and cell cycle regulation. The DDB1 subunit is a target for the hepatitis B virus X protein (HBx). Binding of HBx to DDB1 interferes with cell growth and viability in culture and has been implicated in the establishment of viral infection. DDB1 also interacts with the V proteins encoded by several paramyxoviruses including simian virus 5 (SV5), which prevent interferon signaling by targeting either STAT1 or STAT2 proteins for proteolysis. The role of V binding to DDB1, however, remains unclear. Here we show that the V protein of SV5 (SV5-V) and HBx exhibit strikingly similar DDB1 binding properties. Thus, SV5-V and HBx bind to DDB1 in a mutually exclusive manner, and SV5-V shares with HBx the ability to enhance the steady-state levels of DDB1 and to inhibit its association with DDB2. Yet only HBx induces cell death, and SV5-V can prevent HBx from doing so by blocking its interaction with DDB1. Binding of SV5-V to DDB1 may serve another function, since SV5-V shows a decreased ability to induce STAT1 degradation in cells expressing reduced amounts of DDB1. These findings demonstrate that HBx performs a unique function through its association with DDB1 for which SV5-V cannot substitute and suggest that SV5-V and HBx have evolved to bind DDB1 to achieve distinct functions, both by a mechanism that does not involve DDB2.
Department of Genetics and Microbiology, University Medical Centre (C.M.U.), 1211 Geneva 4, Switzerland.
Olivier
O
Leupin
Séverine
S
Bontron
Michel
M
Strubin
D017209:Apoptosis; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D019213:Rubulavirus / Q000502:physiology*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins / Q000378:metabolism*
C091435:DDB1 protein, human; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; C097019:V protein, Simian parainfluenza virus 5; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins; C057628:hepatitis B virus X protein