The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa, 3200003, Israel.
The Fred Wyszkowski Cancer Research Laboratory, Dept. of Biology, Technion-Israel Institute of Technology, Haifa, 3200003, Israel.
Drug Resist Updat. 2020 Dec;53:100729. doi: 10.1016/j.drup.2020.100729. Epub 2020 Oct 7.
Histone modifications and more specifically ε-lysine acylations are key epigenetic regulators that control chromatin structure and gene transcription, thereby impacting on various important cellular processes and phenotypes. Furthermore, lysine acetylation of many non-histone proteins is involved in key cellular processes including transcription, DNA damage repair, metabolism, cellular proliferation, mitosis, signal transduction, protein folding, and autophagy. Acetylation affects protein functions through multiple mechanisms including regulation of protein stability, enzymatic activity, subcellular localization, crosstalk with other post-translational modifications as well as regulation of protein-protein and protein-DNA interactions. The paralogous lysine acetyltransferases KAT6A and KAT6B which belong to the MYST family of acetyltransferases, were first discovered approximately 25 years ago. KAT6 acetyltransferases acylate both histone H3 and non-histone proteins. In this respect, KAT6 acetyltransferases play key roles in regulation of transcription, various developmental processes, maintenance of hematopoietic and neural stem cells, regulation of hematopoietic cell differentiation, cell cycle progression as well as mitosis. In the current review, we discuss the physiological functions of the acetyltransferases KAT6A and KAT6B as well as their functions under pathological conditions of aberrant expression, leading to several developmental syndromes and cancer. Importantly, both upregulation and downregulation of KAT6 proteins was shown to play a role in cancer formation, progression, and therapy resistance, suggesting that they can act as oncogenes or tumor suppressors. We also describe reciprocal regulation of expression between KAT6 proteins and several microRNAs as well as their involvement in cancer formation, progression and resistance to therapy.
组蛋白修饰，尤其是 ε-赖氨酸酰化，是控制染色质结构和基因转录的关键表观遗传调控因子，从而影响各种重要的细胞过程和表型。此外，许多非组蛋白的赖氨酸乙酰化参与关键的细胞过程，包括转录、DNA 损伤修复、代谢、细胞增殖、有丝分裂、信号转导、蛋白质折叠和自噬。乙酰化通过多种机制影响蛋白质功能，包括调节蛋白质稳定性、酶活性、亚细胞定位、与其他翻译后修饰的串扰以及调节蛋白质-蛋白质和蛋白质-DNA 相互作用。属于 MYST 乙酰转移酶家族的赖氨酸乙酰转移酶 KAT6A 和 KAT6B 是大约 25 年前首次发现的。KAT6 乙酰转移酶酰化组蛋白 H3 和非组蛋白蛋白。在这方面，KAT6 乙酰转移酶在转录调控、各种发育过程、造血和神经干细胞的维持、造血细胞分化的调节、细胞周期进程以及有丝分裂中发挥关键作用。在当前的综述中，我们讨论了乙酰转移酶 KAT6A 和 KAT6B 的生理功能及其在异常表达的病理条件下的功能，导致几种发育综合征和癌症。重要的是，KAT6 蛋白的上调和下调都被证明在癌症的形成、进展和耐药性中发挥作用，表明它们可以作为癌基因或肿瘤抑制因子。我们还描述了 KAT6 蛋白和几种 microRNA 之间表达的相互调节及其在癌症形成、进展和对治疗的耐药性中的参与。
