Regulatory effects of post-translational modifications on zDHHC S-acyltransferases.
Regulatory effects of post-translational modifications on zDHHC S-acyltransferases.
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翻译后修饰对zDHHC S-酰基转移酶的调节作用。
DOI：
10.1074/jbc.rev120.014717
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发表时间：
2020-10-23
期刊：
影响因子：
--
通讯作者：
Chamberlain LH
中科院分区：
文献类型：
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作者：
Zmuda F;Chamberlain LH
人zDHHC S-酰基转移酶家族包括23种酶，其介导多种细胞蛋白的S-酰化，包括通道、受体、转运蛋白、信号传导分子、支架和分子伴侣。这种可逆的过渡后修饰（PTM）涉及将通常衍生自棕榈酰辅酶A的脂肪酰基链连接到靶蛋白上的特定半胱氨酸残基，这会影响其稳定性、定位和功能。这些结果对于控制许多过程至关重要，包括突触传递和可塑性，细胞生长和分化以及病毒和其他病原体的感染性。鉴于S-酰化的生理重要性，这是不足为奇的，在这个过程中的扰动，包括ZDHHC基因的突变，已与不同的神经病理和癌症，并有越来越多的兴趣zDHHC酶作为新的药物靶标。虽然zDHHC酶控制着各种各样的细胞过程，并与主要疾病有关，但我们对这些酶的理解令人惊讶地不完整，特别是关于控制这些酶的调节机制。然而，越来越多的证据强调了不同PTM在这一过程中的作用。在这篇综述中，我们讨论了如何PTM，包括磷酸化，S-酰化，和泛素化，影响zDHHC酶的稳定性，定位和功能，并推测可能的影响PTM已经出现了较大的筛选研究。更好地了解PTM对zDHHC酶的调节作用将为S-酰化的细胞内动力学提供新的见解，也可能突出调节S-酰化以获得临床收益的新方法。
The human zDHHC S-acyltransferase family comprises 23 enzymes that mediate the S-acylation of a multitude of cellular proteins, including channels, receptors, transporters, signaling molecules, scaffolds, and chaperones. This reversible post-transitional modification (PTM) involves the attachment of a fatty acyl chain, usually derived from palmitoyl-CoA, to specific cysteine residues on target proteins, which affects their stability, localization, and function. These outcomes are essential to control many processes, including synaptic transmission and plasticity, cell growth and differentiation, and infectivity of viruses and other pathogens. Given the physiological importance of S-acylation, it is unsurprising that perturbations in this process, including mutations in ZDHHC genes, have been linked to different neurological pathologies and cancers, and there is growing interest in zDHHC enzymes as novel drug targets. Although zDHHC enzymes control a diverse array of cellular processes and are associated with major disorders, our understanding of these enzymes is surprisingly incomplete, particularly with regard to the regulatory mechanisms controlling these enzymes. However, there is growing evidence highlighting the role of different PTMs in this process. In this review, we discuss how PTMs, including phosphorylation, S-acylation, and ubiquitination, affect the stability, localization, and function of zDHHC enzymes and speculate on possible effects of PTMs that have emerged from larger screening studies. Developing a better understanding of the regulatory effects of PTMs on zDHHC enzymes will provide new insight into the intracellular dynamics of S-acylation and may also highlight novel approaches to modulate S-acylation for clinical gain.