1. Targeting autophagy-related protein kinases for potential therapeutic purpose
- Author
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Jifa Zhang, Bo Liu, Liang Ouyang, Honggang Xiang, Congcong Lin, and Lan Zhang
- Subjects
PINK1, PTEN-induced putative kinase 1 ,Review ,PROTAC, proteolysis targeting chimeras ,PTMs, post-translational modifications ,Protein aggregation ,PKCα, protein kinase C alpha type ,AKT1, AKT serine/threonine kinase 1 ,PD, Parkinson's disease ,Autophagy-related kinase ,DAPK, death associated protein kinase ,PKD1, polycystin-1 ,GAP, GTPase-activating protein ,PKACα, a protein kinase cAMP-activated catalytic subunit alpha ,0302 clinical medicine ,Human disease ,TNBC - Triple-negative breast cancer ,Protein kinases ,LC3, microtubule-associated protein 1 light chain 3 ,UVRAG, ultraviolet resistance-associated gene ,TFEB, transcription factor EB ,Phosphorylation ,General Pharmacology, Toxicology and Pharmaceutics ,Rheb, the RAS homolog enriched in brain ,TAK1, transforming growth factor activated kinase-1 ,0303 health sciences ,Kinase ,mTORC1, mammalian target of rapamycin complex 1 ,PI3 kinase, phosphoinositide 3-kinase ,Cell biology ,GSK3α, glycogen synthase kinase 3 alpha ,HMGB1, high mobility group protein B1 ,AMBRA1, autophagy/beclin-1 regulator 1 ,ULK complex, ULK1–mATG13–FIP200–ATG101 complex ,ARF, auxin response factor gene ,030220 oncology & carcinogenesis ,TSC1/2, tuberous sclerosis complex proteins 1/2 ,PIM2, proviral insertion in murine lymphomas 2 ,LPS, lipopolysaccharide ,PI3P, phosphatidylinositol triphosphate ,Small-molecule kinase inhibitors/activators ,JNK1, C-Jun N-terminal kinase ,mTOR, mammalian target of rapamycin ,ULK1, unc-51-like kinase 1 ,Biology ,PPIs, protein–protein interactions ,PI, phosphatidylinositol ,TNBC, triple-negative breast cancer ,FIP200, FAK family kinase-interacting protein of 200 kDa ,03 medical and health sciences ,4E-BP1, eukaryotic translation initiation factor 4E-binding protein ,Organelle ,Autophagy ,LRRK2, leucine rich repeat kinase 2 ,ATG, autophagy-related protein ,GO, gene ontology ,030304 developmental biology ,PD - Parkinson's disease ,lcsh:RM1-950 ,CaMKK2, calcium/calmodulin-dependent protein kinase kinase 2 ,Human disease therapy ,AMPK, AMP-activated protein kinase ,lcsh:Therapeutics. Pharmacology ,PIP2, phosphatidylinositol-4,5-bisphosphate ,LKB1, serine/threonine-protein kinase stk11 - Abstract
Autophagy, defined as a scavenging process of protein aggregates and damaged organelles mediated by lysosomes, plays a significant role in the quality control of macromolecules and organelles. Since protein kinases are integral to the autophagy process, it is critically important to understand the role of kinases in autophagic regulation. At present, intervention of autophagic processes by small-molecule modulators targeting specific kinases has becoming a reasonable and prevalent strategy for treating several varieties of human disease, especially cancer. In this review, we describe the role of some autophagy-related kinase targets and kinase-mediated phosphorylation mechanisms in autophagy regulation. We also summarize the small-molecule kinase inhibitors/activators of these targets, highlighting the opportunities of these new therapeutic agents., Graphical abstract This review elaborates in detail the role of some autophagy-related kinase targets and phosphorylation in autophagy regulation, and further summarizes the application of small-molecule kinase inhibitors/activators for autophagy inhibition and induction. Understanding how these autophagy-related kinases regulate autophagy machinery is critical for the potential therapeutic application of autophagy.Image 1
- Published
- 2020