UNC-51-like Kinase 1: From an Autophagic Initiator to Multifunctional Drug Target

被引：33

作者：

Zhang, Lan

Ouyang, Liang

Guo, Yongzhi

Zhang, Jin

Liu, Bo ^{[1
]}

机构：

[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 15期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

CELL-DEATH; INFLAMMASOME ACTIVATION; ULK1; UBIQUITYLATION; INTERACTING PROTEIN; VPS34; COMPLEXES; PHOSPHORYLATION; MTORC1; IDENTIFICATION; INHIBITION; ASSOCIATION;

D O I：

10.1021/acs.jmedchem.7b01684

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

UNC-51-like kinase 1 (ULK1), known as an ortholog of the yeast Atgl, 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.

引用

页码：6491 / 6500

页数：10

共 67 条

[61] ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy [J].