Abstract：
In the case of small-cell lung carcinoma, the highly metastatic nature of the disease and the propensity for several chromatin modifiers to harbor mutations suggest that epigenetic manipulation may also be a promising route for oncotherapy, but histone deacetylase inhibitors on their own do not appear to be particularly effective, suggesting that there may be other regulatory parameters that dictate the effectiveness of vorinostat\'s reversal of histone deacetylation. Recent discoveries that serotonylation of histone H3 alters the permissibility of gene expression have led to renewed attention to this rare modification, as facilitated by transglutaminase 2, and at the same time introduce new questions about whether this modification belongs to a part of the concerted cohort of regulator events for modulating the epigenetic landscape. This review explores the mechanistic details behind protein serotonylation and its possible connections to the epigenome via histone modifications and glycan interactions and attempts to elucidate the role of transglutaminase 2, such that optimizations to existing histone deacetylase inhibitor designs or combination therapies may be devised for lung and other types of cancer.
摘要：
在小细胞肺癌的情况下，该疾病的高度转移性和几种染色质修饰剂对港口突变的倾向表明，表观遗传操纵也可能是肿瘤治疗的有希望的途径。但组蛋白去乙酰化酶抑制剂本身似乎并不是特别有效，这表明可能还有其他调节参数决定伏立诺他逆转组蛋白去乙酰化的有效性。最近发现组蛋白H3的血清素化改变了基因表达的可容许性，这引起了人们对这种罕见修饰的重新关注。正如转谷氨酰胺酶2所促进的那样，同时引入了新的问题，即这种修饰是否属于调节表观遗传景观的调节事件的协调队列的一部分。这篇综述探讨了蛋白质5-羟色胺化背后的机制细节及其通过组蛋白修饰和聚糖相互作用与表观基因组的可能连接，并试图阐明转谷氨酰胺酶2的作用，从而优化现有的组蛋白脱乙酰酶抑制剂设计或组合疗法可能被设计用于肺癌和其他类型的癌症。
