Identification of lysines 36 and 37 of PARP-2 as targets for acetylation and auto-ADP-ribosylation
Identification of lysines 36 and 37 of PARP-2 as targets for acetylation and auto-ADP-ribosylation
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DOI：
10.1016/j.biocel.2008.03.008
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Hottiger, Michael O.
中科院分区：
文献类型：
--
作者：
Haenni, Sandra S.;Hassa, Paul O.;Hottiger, Michael O.
聚adp -核糖聚合酶-2 （PARP-2）被描述为通过共同调节不同的转录因子来调节细胞功能，包括DNA监视，炎症和细胞分化。通过体外和体内实验，我们发现PARP-2是组蛋白乙酰转移酶PCAF和GCN5L的新底物。位点定向诱变表明，位于PARP-2核定位信号中的赖氨酸36和37是体外PCAF和GCN5L活性的主要靶点。有趣的是，相同的两个PARP-2残基的乙酰化降低了PARP-2的DNA结合和酶活性。最后，与野生型PARP-2相比，赖氨酸36和37突变的PARP-2显示出自身单adp核糖基化减少。总之，我们的研究结果提供了证据，证明PARP-2的乙酰化是一个关键的翻译后修饰，可以调节DNA结合，从而也调节PARP-2的酶活性。(c) 2008 Elsevier Ltd.版权所有。
Poly-ADP-ribose polymerase-2 (PARP-2) was described to regulate cellular functions comprising DNA surveillance, inflammation and cell differentiation by co-regulating different transcription factors. Using an in vitro and in vivo approach, we identified PARP-2 as a new substrate for the histone acetyltransferases PCAF and GCN5L. Site directed mutagenesis indicated that lysines 36 and 37, located in the nuclear localization signal of PARP-2, are the main targets for PCAF and GCN5L activity in vitro. Interestingly, acetylation of the same two PARP-2 residues reduces the DNA binding and enzymatic activity of PARP-2. Finally, PARP-2 with mutated lysines 36 and 37 showed reduced auto-mono-ADP-ribosylation when compared to wild type PARP-2. Together, our results provide evidence that acetylation of PARP-2 is a key post-translational modification that may regulate DNA binding and consequently also the enzymatic activity of PARP-2. (c) 2008 Elsevier Ltd. All rights reserved.