Poly (ADP-Ribose) Polymerase-1 Binds to BCL2 Major Breakpoint Region and Regulates BCL2 Expression

BCL2, originally identified as a proto-oncogene in B-cell lymphoma, is a key regulator of apoptosis Although it is more than 200 kb in length, at least 70% of the t(14;18) translocation in follicular lymphomas occurs at the BCL2 major breakpoint region (mbr), located in the 3'-untranslated region (3'-UTR) We have previously found that the mbr is a regulatory element which positively regulates BCL2 expression and this regulatory function was closely associated with SATB1, which binds to a 37 bp mbr (37 mbr) in the 3'-end of the mbr directly However, the precise molecular mechanisms by which the mbr regulates gene expression are not fully understood. In this study, we purified Poly(ADP-ribose) polymerase-1 (PARP-1) from the DNA-protein complexes formed by 37 mbr in Jurkat cells and demonstrated that PARP-1 participates in the 37 mbr-protein complex's formation in vitro and in vivo Functional analysis showed that overexpression of PARP-1 decreases 37 mbr regulatory function and BCL2 expression Conversely, knockdown of PARP-1 with RNAi increases BCL2 expression. Taken together, the present findings indicate that PARP-1 is a component of BCL2 37 mbr-protein complexes, and PARP-1 is involved in the regulation of BCL2 expression These findings are helpful in understanding the regulatory mechanisms of BCL2 expression J. Cell Biochem 110 1208-1218, 2010 (C) 2010 Wiley-Liss, Inc