Koeberle Andreas, Löser Konstantin, Thürmer Maria
Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, 07743 Jena, Germany.
Biochim Biophys Acta. 2016 Nov;1861(11):1719-1726. doi: 10.1016/j.bbalip.2016.08.009. Epub 2016 Aug 24.
Stearoyl-CoA desaturase (SCD), the central enzyme in the biosynthesis of monounsaturated fatty acids, introduces a cis-Δ9 double bond into saturated fatty acids. SCD-1 has been proposed as promising target for the treatment of cancer, skin disorders and metabolic diseases, and strong efforts have been made during the last decade to develop clinical drug candidates. While the regulation and biological implications of SCD-1 have been extensively reviewed, the molecular mechanisms through which SCD-1 mediates cellular responses remained a mystery. An important aspect seems to be that SCD-1 induces adaptive stress signaling that maintains cellular persistence and fosters survival and cellular functionality under distinct pathological conditions. Here, we will first provide an overview about the function, regulation, structure and mechanism of SCD-1 and then focus on mitogenic and stress-related signal transduction pathways orchestrated by SCD-1. Moreover, we will discuss molecular mechanisms and potential lipid factors that link SCD-1 activity with initial signal transduction.
硬脂酰辅酶A去饱和酶(SCD)是单不饱和脂肪酸生物合成中的关键酶,它将顺式Δ9双键引入饱和脂肪酸中。SCD-1已被认为是治疗癌症、皮肤疾病和代谢疾病的有前景的靶点,在过去十年中人们付出了巨大努力来开发临床候选药物。虽然SCD-1的调节和生物学意义已得到广泛综述,但SCD-1介导细胞反应的分子机制仍是个谜。一个重要方面似乎是SCD-1诱导适应性应激信号,这种信号在不同病理条件下维持细胞持久性并促进存活和细胞功能。在这里,我们首先将概述SCD-1的功能、调节、结构和机制,然后重点关注由SCD-1精心编排的促有丝分裂和应激相关信号转导途径。此外,我们将讨论将SCD-1活性与初始信号转导联系起来的分子机制和潜在脂质因子。