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KATs 的多重人生——细胞环境的探测器、整合者和调节剂。

The many lives of KATs - detectors, integrators and modulators of the cellular environment.

机构信息

Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.

出版信息

Nat Rev Genet. 2019 Jan;20(1):7-23. doi: 10.1038/s41576-018-0072-4.

Abstract

Research over the past three decades has firmly established lysine acetyltransferases (KATs) as central players in regulating transcription. Recent advances in genomic sequencing, metabolomics, animal models and mass spectrometry technologies have uncovered unexpected new roles for KATs at the nexus between the environment and transcriptional regulation. Thousands of reversible acetylation sites have been mapped in the proteome that respond dynamically to the cellular milieu and maintain major processes such as metabolism, autophagy and stress response. Concurrently, researchers are continuously uncovering how deregulation of KAT activity drives disease, including cancer and developmental syndromes characterized by severe intellectual disability. These novel findings are reshaping our view of KATs away from mere modulators of chromatin to detectors of the cellular environment and integrators of diverse signalling pathways with the ability to modify cellular phenotype.

摘要

过去三十年来的研究已经明确确立赖氨酸乙酰转移酶(KATs)作为调节转录的核心分子。基因组测序、代谢组学、动物模型和质谱技术的最新进展揭示了 KATs 在环境和转录调节之间的交汇点上具有意想不到的新作用。数以千计的可逆乙酰化位点已经在蛋白质组中被定位,它们对细胞环境做出动态响应,并维持着代谢、自噬和应激反应等主要过程。与此同时,研究人员不断揭示 KAT 活性失调如何导致疾病,包括癌症和以严重智力障碍为特征的发育综合征。这些新发现正在改变我们对 KATs 的看法,将其从仅仅是染色质的调节剂转变为细胞环境的探测器,以及具有改变细胞表型能力的各种信号通路的整合者。

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