title: Poly (ADP-ribose) polymerase-1 binds to BCL2 major breakpoint region and regulates BCL2 expression.
abstract: 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.
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Hanzhong Rd #140, Nanjing, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Feiran
authors.initials: F
authors.lastname: Gong
authors.forename: Luan
authors.initials: L
authors.lastname: Sun
authors.forename: Dapeng
authors.initials: D
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Changyan
authors.initials: C
authors.lastname: Ma
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D056905:Chromosome Breakpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D011065:Poly(ADP-ribose) Polymerases