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
收藏
页码：6491 / 6500
页数：10
相关论文
共 67 条
  • [1] Baicalein induces autophagic cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human cancer cells
    Aryal, Pramod
    Kim, Kijoong
    Park, Pil-Hoon
    Ham, Seongho
    Cho, Junghee
    Song, Kyung
    [J]. FEBS JOURNAL, 2014, 281 (20) : 4644 - 4658
  • [2] Autophagy Induction by Histone Deacetylase Inhibitors Inhibits HIV Type 1
    Campbell, Grant R.
    Bruckman, Rachel S.
    Chu, Yen-Lin
    Spector, Stephen A.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290 (08) : 5028 - 5040
  • [3] UNC51-like kinase 1, autophagic regulator and cancer therapeutic target
    Chen, Y.
    He, J.
    Tian, M.
    Zhang, S. -Y.
    Guo, M. -R.
    Kasimu, R.
    Wang, J. -H.
    Ouyang, L.
    [J]. CELL PROLIFERATION, 2014, 47 (06) : 494 - 505
  • [4] Identification of ULK1 as a novel biomarker involved in miR-4487 and miR-595 regulation in neuroblastoma SH-SY5Y cell autophagy
    Chen, Yi
    Wang, Shuya
    Zhang, Lan
    Xie, Tao
    Song, Sicheng
    Huang, Jian
    Zhang, Yonghui
    Ouyang, Liang
    Liu, Bo
    [J]. SCIENTIFIC REPORTS, 2015, 5
  • [5] The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy
    Di Bartolomeo, Sabrina
    Corazzari, Marco
    Nazio, Francesca
    Oliverio, Serafina
    Lisi, Gaia
    Antonioli, Manuela
    Pagliarini, Vittoria
    Matteoni, Silvia
    Fuoco, Claudia
    Giunta, Luigi
    D'Amelio, Marcello
    Nardacci, Roberta
    Romagnoli, Alessandra
    Piacentini, Mauro
    Cecconi, Francesco
    Fimia, Gian Maria
    [J]. JOURNAL OF CELL BIOLOGY, 2010, 191 (01) : 155 - 168
  • [6] The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs
    Dite, Toby A.
    Ling, Naomi X. Y.
    Scott, John W.
    Hoque, Ashfaqul
    Galic, Sandra
    Parker, Benjamin L.
    Ngoei, Kevin R. W.
    Langendorf, Christopher G.
    O'Brien, Matthew T.
    Kundu, Mondira
    Viollet, Benoit
    Steinberg, Gregory R.
    Sakamoto, Kei
    Kemp, Bruce E.
    Oakhill, Jonathan S.
    [J]. NATURE COMMUNICATIONS, 2017, 8
  • [7] Deubiquitinase inhibition by WP1130 leads to ULK1 aggregation and blockade of autophagy
    Driessen, Stefan
    Berleth, Niklas
    Friesen, Olena
    Loeffler, Antje S.
    Boehler, Philip
    Hieke, Nora
    Stuhldreier, Fabian
    Peter, Christoph
    Schink, Kay O.
    Schultz, Sebastian W.
    Stenmark, Harald
    Holland, Petter
    Simonsen, Anne
    Wesselborg, Sebastian
    Stork, Bjoern
    [J]. AUTOPHAGY, 2015, 11 (09) : 1458 - 1470
  • [8] FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation
    Dunlop, Elaine A.
    Seifan, Sara
    Claessens, Tijs
    Behrends, Christian
    Kamps, Miriam A. F.
    Rozycka, Ewelina
    Kemp, Alain J.
    Nookala, Ravi K.
    Blenis, John
    Coull, Barry J.
    Murray, James T.
    van Steensel, Maurice A. M.
    Wilkinson, Simon
    Tee, Andrew R.
    [J]. AUTOPHAGY, 2014, 10 (10) : 1749 - 1760
  • [9] ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding
    Dunlop, Elaine A.
    Hunt, David K.
    Acosta-Jaquez, Hugo A.
    Fingar, Diane C.
    Tee, Andrew R.
    [J]. AUTOPHAGY, 2011, 7 (07) : 737 - 747
  • [10] Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates
    Egan, Daniel F.
    Chun, Matthew G. H.
    Vamos, Mitchell
    Zou, Haixia
    Rong, Juan
    Miller, Chad J.
    Lou, Hua Jane
    Raveendra-Panickar, Dhanya
    Yang, Chih-Cheng
    Sheffler, Douglas J.
    Teriete, Peter
    Asara, John M.
    Turk, Benjamin E.
    Cosford, Nicholas D. P.
    Shaw, Reuben J.
    [J]. MOLECULAR CELL, 2015, 59 (02) : 285 - 297
1234567