The post-translational modifications of proliferating cell nuclear antigen - Acetylation, not phosphorylation, plays an important role in the regulation of its function
The post-translational modifications of proliferating cell nuclear antigen - Acetylation, not phosphorylation, plays an important role in the regulation of its function
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DOI：
10.1074/jbc.m312850200
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发表时间：
2004-05-07
影响因子：
4.8
通讯作者：
Lee, H
中科院分区：
文献类型：
--
作者：
Naryzhny, SN;Lee, H
增殖细胞核抗原（PCNA）的多种功能被认为是由于，在很大程度上，翻译后修饰。在这里，我们显示了高分辨率的二维PAGE分析，有三个不同的PCNA亚型，不同的乙酰化状态。中度乙酰化的主要（M）形式被发现在所有的亚细胞区室的循环细胞，而高度乙酰化的酸性形式主要是在核质，核基质，和染色质中发现。有趣的是，去乙酰化的碱性形式在周期细胞的核质中最为明显。G（0）细胞和周期细胞的胞质中主要只含有M型。由于p300和组蛋白去乙酰化酶（HDAC 1）与PCNA免疫共沉淀，它们可能分别负责PCNA的乙酰化和去乙酰化。我们还发现去乙酰化降低了PCNA与DNA聚合酶β和δ结合的能力。总之，我们的数据支持一个模型，其中的酸性和M形式参与DNA复制，而基本形式与DNA复制的终止。
The diverse function of proliferating cell nuclear antigen (PCNA) is thought to be due, in large part, to post-translational modifications. Here we show by high resolution two-dimensional PAGE analysis that there are three distinct PCNA isoforms that differ in their acetylation status. The moderately acetylated main (M) form was found in all of the subcellular compartments of cycling cells, whereas the highly acetylated acidic form was primarily found in the nucleoplasm, nuclear matrix, and chromatin. Interestingly, the deacetylated basic form was most pronounced in the nucleoplasm of cycling cells. The cells in G(0) and the cytoplasm of cycling cells contained primarily the M form only. Because p300 and histone deacetylase (HDAC1) were co-immunoprecipitated with PCNA, they are likely responsible for the acetylation and deacetylation of PCNA, respectively. We also found that deacetylation reduced the ability of PCNA to bind to DNA polymerases beta and delta. Taken together, our data support a model where the acidic and M forms participate in DNA replication, whereas the basic form is associated with the termination of DNA replication.