Poly (ADP‐ribose) polymerase‐1 binds to BCL2 major breakpoint region and regulates BCL2 expression
Poly (ADP‐ribose) polymerase‐1 binds to BCL2 major breakpoint region and regulates BCL2 expression
复制标题
DOI：
10.1002/jcb.22635
复制
发表时间：
2010-08
影响因子：
4
通讯作者：
Nan Yang;Feiran Gong;Luan Sun;Dapeng Yang;Xiao Han;Changyan Ma;Yujie Sun
中科院分区：
文献类型：
--
作者：
Nan Yang;Feiran Gong;Luan Sun;Dapeng Yang;Xiao Han;Changyan Ma;Yujie Sun
BCL2最初被认为是B细胞淋巴瘤的原癌基因，是细胞凋亡的关键调控因子。尽管其长度超过200 kb，但滤泡性淋巴瘤中至少70%的t（14;18）易位发生在位于3′‐非翻译区（3′‐UTR）的BCL2主要断点区（mbr）。我们之前已经发现mbr是一个正向调节BCL2表达的调控元件，并且这种调控功能与SATB1密切相关，SATB1直接结合在mbr的3 '‐端一个37 bp的mbr （37 mbr）上。然而，mbr调控基因表达的精确分子机制尚不完全清楚。在这项研究中，我们从Jurkat细胞中37mbr形成的dna -蛋白复合物中纯化了聚（ADP核糖）聚合酶- 1 (PARP‐1)，并证明PARP‐1在体内和体外参与了37mbr -蛋白复合物的形成。功能分析显示，PARP‐1过表达降低了37mbr的调控功能和BCL2的表达。相反，用RNAi敲低PARP‐1会增加BCL2的表达。综上所述，目前的研究结果表明，PARP‐1是BCL2 37mbr蛋白复合物的一个组成部分，并且PARP‐1参与BCL2表达的调控。这些发现有助于理解BCL2表达的调控机制。j .细胞。中国生物医学工程学报，2010,31(2):481 - 481。出版于2010年Wiley‐Liss， Inc。
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. Published 2010 Wiley‐Liss, Inc.