State Key Laboratory of Biotherapy and Cancer Center, West China Hospital , Sichuan University and Collaborative Innovation Center of Biotherapy , Chengdu 610041 , China.
J Med Chem. 2018 Aug 9;61(15):6491-6500. doi: 10.1021/acs.jmedchem.7b01684. Epub 2018 Mar 14.
UNC-51-like kinase 1 (ULK1), known as an ortholog of the yeast Atg1, is the serine-threonine kinase and the autophagic initiator in mammals. Accumulating evidence has recently revealed the kinase domain structure of ULK1 and its post-translational modifications, as well as further elucidated its regulatory autophagic pathways and associations with diverse human diseases. Interestingly, a series of small molecules have been recently reported to target ULK1 or ULK1-modulating autophagy, which may provide a clue on exploiting them as novel candidate drugs. Taken together, this review discusses how ULK1 acts as an autophagic initiator for modulation of its intricate mechanisms, as well as how ULK1 becomes a multifunctional target for potential therapeutic applications.
UNC-51 样激酶 1(ULK1),作为酵母 Atg1 的同源物,是哺乳动物中丝氨酸/苏氨酸激酶和自噬的起始因子。最近的大量证据揭示了 ULK1 的激酶结构域及其翻译后修饰,以及进一步阐明了其调节自噬的途径及其与多种人类疾病的关联。有趣的是,最近有一系列小分子被报道可以靶向 ULK1 或调节自噬的 ULK1,这可能为利用它们作为新型候选药物提供了线索。综上所述,本综述讨论了 ULK1 如何作为自噬的起始因子来调节其复杂的机制,以及 ULK1 如何成为多功能的潜在治疗应用靶标。