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Targeting autophagy-related protein kinases for potential therapeutic purpose

Authors :
Jifa Zhang
Bo Liu
Liang Ouyang
Honggang Xiang
Congcong Lin
Lan Zhang
Source :
Acta Pharmaceutica Sinica B, Vol 10, Iss 4, Pp 569-581 (2020), Acta Pharmaceutica Sinica. B
Publication Year :
2020
Publisher :
Elsevier, 2020.

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.<br />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

Subjects

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

Details

Language :
English
ISSN :
22113835
Volume :
10
Issue :
4
Database :
OpenAIRE
Journal :
Acta Pharmaceutica Sinica B
Accession number :
edsair.doi.dedup.....e2e45bf1ac401222740c4f8e78dae670