B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity
B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity
复制标题
DOI：
10.1074/jbc.m505408200
复制
发表时间：
2005-10-07
影响因子：
4.8
通讯作者：
Shipp, MA
中科院分区：
文献类型：
--
作者：
Aguiar, RCT;Takeyama, K;Shipp, MA
BAL 1（B-aggressive lymphoma 1）最初被鉴定为弥漫性大B细胞淋巴瘤的风险相关基因。BAL 1编码一种核蛋白，具有N-末端大结构域和一个假定的C-末端聚（ADP-核糖）聚合酶（PARP）活性位点。宏结构域是与组蛋白macroH 2A的非组蛋白区域同源的序列。一些证据表明，这些结构域可以调节转录，包括在失活X染色体中高浓度的组蛋白macroH 2A，直接干扰定位核小体中的转录因子结合，以及与DNA结合结构域的结构相似性。多聚腺苷二磷酸核糖基化是一种重要的翻译后修饰，调节染色质构型和转录。在这份报告中，我们描述了另外两个BAL家族成员，BAL 2和BAL 3，与N-末端宏域和推定的C-末端PARP活性位点，并评估这些特定区域的功能在BAL家族成员。在此，我们证明了BAL宏结构域在与启动子连接时抑制转录。此外，我们发现BAL 2和BAL 3，而不是BAL 1，表现出PARP活性。与这些数据一致，BAL 1缺乏在BAL 2和-3 PARP活性位点中保守的几个关键供体和受体残基。感兴趣的是，具有失活或功能性PARP结构域的BAL家族成员抑制转录的能力不同。BAL家族成员是唯一描述的具有PARP和宏结构域的蛋白质，强调了这种独特组合的潜在功能意义。
BAL1 (B-aggressive lymphoma 1) was originally identified as a risk- related gene in diffuse large B-cell lymphoma. BAL1 encodes a nuclear protein with N-terminal macro domains and a putative C-terminal poly( ADP-ribose) polymerase ( PARP) active site. Macro domains are sequences homologous to the non-histone region of histone macroH2A. Several lines of evidence suggest that these domains may modulate transcription, including a high concentration of histone macroH2A in the inactive X chromosome, direct interference with transcription factor binding in a positioned nucleosome, and structural similarity to DNA binding domains. Poly( ADP-ribosyl) ation is a critical post-translational modification that regulates chromatin configuration and transcription. In this report we describe two additional BAL family members, BAL2 and BAL3, with N-terminal macro domains and putative C-terminal PARP active sites and assess the function of these specific regions in BAL family members. Herein, we demonstrate that BAL macro domains repress transcription when tethered to a promoter. In addition, we show that BAL2 and BAL3, but not BAL1, exhibit PARP activity. In agreement with these data, BAL1 lacks several critical donor and acceptor residues that are conserved in the BAL2 and -3 PARP active sites. Of interest, BAL family members with inactive or functional PARP domains differed in their ability to repress transcription. BAL family members are the only described proteins with both PARP and macro domains, underscoring the potential functional significance of this unique combination.