Buchwald Marc, Krämer Oliver H, Heinzel Thorsten
Center for Molecular Biomedicine, Institute for Biochemistry and Biophysics, Friedrich-Schiller-Universität Jena, Jena, Germany.
Cancer Lett. 2009 Aug 8;280(2):160-7. doi: 10.1016/j.canlet.2009.02.028. Epub 2009 Apr 1.
Histone deacetylases (HDACs) play an important role in gene regulation. Inhibitors of HDACs (HDACi) are novel anti-cancer drugs, which induce histone (hyper-) acetylation and counteract aberrant gene repression. On the other hand, HDACi treatment can also result in decreased gene expression, and targeting HDACs affects more than chromatin. Recently, HDACi were shown to evoke non-histone protein acetylation, which can alter signaling networks relevant for tumorgenesis. Furthermore, HDACi can promote the degradation of (proto-) oncoproteins. Here, we summarize these findings and discuss how these substances could be beneficial for the treatment and prevention of human ailments, such as cancer and unbalanced immune functions.
组蛋白去乙酰化酶(HDACs)在基因调控中发挥着重要作用。HDACs抑制剂(HDACi)是新型抗癌药物,可诱导组蛋白(超)乙酰化并对抗异常的基因抑制。另一方面,HDACi治疗也可能导致基因表达降低,并且靶向HDACs的影响不止于染色质。最近,HDACi被证明可引发非组蛋白的乙酰化,这可能会改变与肿瘤发生相关的信号网络。此外,HDACi可促进(原)癌蛋白的降解。在此,我们总结这些发现,并讨论这些物质如何有益于治疗和预防人类疾病,如癌症和免疫功能失衡。