Acetylation as a transcriptional control mechanism-HDACs and HATs in pancreatic ductal adenocarcinoma.
Acetylation as a transcriptional control mechanism-HDACs and HATs in pancreatic ductal adenocarcinoma.
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DOI：
10.1007/s12029-011-9257-1
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发表时间：
2011-06-01
影响因子：
1.6
通讯作者：
Saur, Dieter
中科院分区：
文献类型：
--
作者：
Schneider, Gunter;Kramer, Oliver H;Saur, Dieter
简介：胰腺导管腺癌（PDAC）是最恶性的肿瘤之一，预后较差。尽管我们对该疾病的致癌作用的认识不断增加，但尚不存在有效的保守治疗策略。因此，必须在实验水平上确定新的目标。组蛋白脱乙酰酶 (HDAC)，尤其是 I 类同工酶 HDAC1、2 和 3，在 PDAC 中高表达。结论：本文总结了 HDAC 同工酶在 PDAC 中的表达和功能，特别关注其启动子特异性作用模式。尽管我们对 PDAC 中的 HDAC 功能有了一些分子上的了解，但对组蛋白乙酰转移酶 (HAT) 在 PDAC 中的相关性知之甚少。作为一个例子，我们将总结 HAT p300 的功能，最近描述了其启动子特异性功能。增加对 PDAC 中乙酰化和脱乙酰化机制功能的分子洞察非常重要，因为这将在未来带来新的基于合理的治疗策略。
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a dismal prognosis. Although our understanding of the carcinogenesis of the disease increases continuously, no effective conservative therapeutic strategies exist. Therefore, novel targets have to be defined at the experimental level. Histone deacetylases (HDACs), especially the class I isoenzymes HDAC1, 2, and 3, are highly expressed in PDAC.CONCLUSION: This article summarizes the expression and functions of HDAC isoenzymes in PDAC, with a special focus on their promoter-specific mode of action. Although we have gained some molecular insight into the HDAC function in PDAC, less is known about the relevance of histone acetyltransferases (HATs) in PDAC. As an example, we will summarize function of the HAT p300, for which promoter-specific functions were described recently. Increasing the molecular insights into the functions of the acetylating and deacetylating machineries in PDAC are important, since this will lead to novel rationally based therapeutic strategies in the future.