BAG-1, a novel Bcl-2-interacting protein, activates expression of human JCvirus

Transcription of the human polyomavirus JC virus (ICV) genome is regulated by cellular proteins and the large tumour (T) antigen. Earlier studies led to the identification of nuclear factor-1 (NF-1)-binding sites in the ICV e nhancer by DNase I protection assays of extracts from retinoic acid (RA)-di fferentiated P19 embryonal carcinoma (EC) cells. In this study, a cDNA clon e that encodes a protein capable of binding to the JCV NF-1 sites was isola ted from an RA-differentiated EC cell cDNA library. Sequence analysis revea led that the cDNA isolated was identical to the previously described Bcl-2- interacting protein BAG-1 (Bcl-2-associated athano gene-1). Results from RN A studies indicated that BAG-1 is expressed in several cell types. Co-trans fection of a recombinant BAG-1 expression plasmid with JCV promoters indica ted that BAG-1 stimulates transcription of the JCV, promoter and to a lesse r extent the JCV, promoter. Mutations in the NF-1 sites in the ICV, promote r eliminated the activation by BAG-1. Thus, BAG-1 is a novel transcription factor that may play a role in JCV expression.