BAG-1M, an isoform of Bcl-2-interacting protein BAG-1, enhances gene expression driven by CMV promoter

BAG-1M, one of the isoforms of BAG-1, was reported to bind to DNA and stimu late general transcription when cells were stressed by heat shock (Zeiner, M., et al., Proc. Natl. Acad. Sci. USA 96, 10194-10199, 1999). Here we show that BAG-IM binds and enhances transcriptional activity of Cytomegalovirus (CMV) early gene promoter under unstressed conditions. This activity is un ique to BAG-1M in that other isoforms, BAG-1S and BAG-1L, are much weaker i n this activity, although all of the isoforms share common ubiquitin-like d omain and BAG domain interacting with Hsp70/Hsc70. Deletion analysis of BAG -1M showed that C-terminal BAG domain is necessary to enhance the CMV promo ter activity, suggesting that interaction with Hsp70/Hsc70 proteins may med iate this function. Another mutation in N-terminus, BAG-1M K(2-4)A, lost DN A binding capacity and majority of the promoter-enhancing activity. Our stu dy demonstrates that both N-terminal DNA binding site and C-terminal Hsp70/ Hsc70 binding site of BAG-1M play an important role in enhancing the CMV pr omoter activity. (C) 2001 Academic Press.