Dissociation of DDB1-binding and transactivation properties of the hepatitis B virus X protein

The hepatitis B virus (HBV)X protein (HBx) is a transactivator encoded by m ammalian hepadnaviruses, and is thought to stimulate transcription by inter acting with one or more host cell factors. Numerous cellular proteins have been reported to interact with HBx including a component of the nucleotide excision repair complex called ultraviolet damaged DNA binding (UV-DDB, or DDB1) protein. Recent studies have identified a role for DDB1 in transcript ion, raising the possibility that HBx may acquire its broad transcriptional properties by interacting with DDB1. A panel of HBx mutant proteins, some of which no longer bind to DDB1, was used to test this hypothesis. Plasmid DNAs encoding HBx wildtype and mutant derivatives were transfected into Hep G2 cells, and their ability to transactivate a cotransfected reporter plasm id tested. Results from the transactivation assays in HepG2 cells were then compared with data obtained from HBx-DDB1 binding studies performed in yea st. Several HBx mutant proteins unable to bind DDB1 remained competent for transactivation, indicating that HBx binding to DDB1 is not required for HB x transactivation of the ETS1 promoter. It remains possible that a subset o f HBx transactivation function targets an as yet undefined DDB1-specific pa thway. (C) 2000 Elsevier Science B.V. All rights reserved.