Role of post translational modifications and novel crosstalk between phosphorylation and O-beta-GlcNAc modifications in human claudin-1,-3 and-4
Role of post translational modifications and novel crosstalk between phosphorylation and O-beta-GlcNAc modifications in human claudin-1,-3 and-4
复制标题
人claudin-1、-3和-4中翻译后修饰的作用以及磷酸化和O-β-GlcNAc修饰之间的新串扰
DOI：
10.1007/s11033-011-0870-7
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发表时间：
2012-02-01
影响因子：
2.8
通讯作者：
Tong, Yigang
中科院分区：
文献类型：
--
作者：
Butt, Azeem Mehmood;Khan, Ishaque Badshah;Tong, Yigang
准确表征翻译后修饰（PTMs）对于理解蛋白质调控机制及其在疾病中的作用非常重要。然而，对PTMs的实验研究，特别是对多功能蛋白的实验研究很难跟踪和研究。因此，生物信息学工具有助于预测关键的蛋白质修饰。为了研究PTMs在claudin蛋白中的作用，特别是claudin-1， -3和-4在人类癌症的发生或进展中，我们对各种PTMs进行了计算机研究并研究了它们的相互作用。鉴于已知cladin的活性受到两种类型的ptm的影响，特别是棕榈酰化和激酶依赖性磷酸化，我们预测cladin -1、-3和-4拓扑结构域中的两个保守区域是潜在的棕榈酰化位点。此外，保守的磷酸化残基可能是激酶的靶标，可以改变claudin维持紧密连接完整性的能力。据我们所知，这是第一个提出claudin蛋白o -糖基化的报告，以及在阴阳位点磷酸化和o -糖基化之间潜在的新相互作用。因此，我们的发现可能促进抗癌药物的生产，并建议新的治疗策略应该针对翻译后事件。
The precise characterization of post translational modifications (PTMs) is important for the understanding of protein regulatory mechanisms and their role in disease. However, experimental studies on PTMs, especially with multifunctional proteins are difficult to follow and investigate. Bioinformatic tools are therefore helpful in predicting key protein modifications. To study the role of PTMs in claudin proteins, specifically claudin-1, -3 and -4 in the onset or progression of human cancers, we performed an in silico study of various PTMs and investigated their interplay. Given that the activity of claudins is known to be influenced by two types of PTMs, specifically palmitoylation and kinase- dependent phosphorylation, we predicted two conserved regions in the topological domains of claudin-1, -3 and -4 as potential palmitoylation sites. Furthermore, conserved phosphorylation residues, which may be targets for kinases and can alter claudin’s ability to maintain the integrity of tight junctions, were identified. To our knowledge, this is the first report to suggest O-glycosylation of claudin proteins, as well as a potential novel interplay between phosphorylation and O-glycosylation at Yin Yang sites. Thus, our findings may facilitate the production of anti-cancer drugs, and suggest that novel therapeutic strategies should target post translational events.