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Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases |
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| Authors: | Fazhao Li Han Xiao Zhiping Hu Fangfang Zhou Binbin Yang |
| Affiliation: | 1. Department of General Surgery, 2nd Xiangya Hospital, Central South University, China;2. Department of Neurology, 2nd Xiangya Hospital, Central South University, China |
| Abstract: | HSPB8 is a member of ubiquitous small heat shock protein (sHSP) family, whose expression is induced in response to a wide variety of unfavorable physiological and environmental conditions. Investigation of HSPB8 structure indicated that HSPB8 belongs to the group of so-called intrinsically disordered proteins and possesses a highly flexible structure. Unlike most other sHSPs, HSPB8 tends to form small-molecular-mass oligomers and exhibits substrate-dependent chaperone activity. In cooperation with BAG3, the chaperone activity of HSPB8 was reported to be involved in the delivery of misfolded proteins to the autophagy machinery. Through this way, HSPB8 interferes with pathological processes leading to neurodegenerative diseases. Accordingly, published studies have identified genetic links between mutations of HSPB8 and some kind of neuromuscular diseases, further supporting its important role in neurodegenerative disorders. In addition to their anti-aggregation properties, HSPB8 is indicated to interact with a wide range of client proteins, modulating their maturations and activities, and therefore, regulates a large repertoire of cellular functions, including apoptosis, proliferation, inflammation and etc. As a result, HSPB8 has key roles in cancer biology, autoimmune diseases, cardiac diseases and cerebral vascular diseases. |
| Keywords: | Aβ amyloid β-peptide ACD α-crystallin domain AD Alzheimer disease ALS amyotrophic lateral sclerosis AR androgen receptor BAG3 BCL2 associated athanogene 3 BMP bone morphogenetic protein CASA chaperone-assisted selective autophagy CHIP C-terminus of Hsc70 interacting protein CK2 casein kinase 2 CMT2L Charcot-Marie-Tooth disease2L CNS central nervous system DC dendrite cell dHMNII2A type II distal hereditary motor neuropathies 2A DPR dipeptide repeat protein DRM desmin-related cardiomyopathy ECM extracellular matrix ER estrogen-receptor FTD frontotemporal dementia GM grey matter GSK glycogen synthase kinase HCHWA-D hereditary cerebral hemorrhage with amyloidosis of the Dutch type HD Huntington Disease HIF-1α hypoxia-inducible factor-1α HSP heat shock protein IDPs intrinsically disordered proteins iNOS inducible isoform of NO synthase IPC ischemic preconditioning I/R ischemia/reperfusion MAPK mitogen-activated protein kinase MMP-9 Matrix Metallopeptidase-9 MS multiple sclerosis MSA multiple system atrophy OGD/R oxygen glucose deprivation/reoxygenation PD Parkinson’s disease PI3K phosphatidylinositol 3′-kinase PK protein kinase PKC-ε protein kinase C-ε PNS peripheral nervous system RA rheumatoid arthritis RBP RNA-binding protein RNP ribonucleoprotein RRE rev response element Sam68 Src associated in mitosis of 68?kDa SBMA spinal and bulbar muscular atrophy SCA3 spinocerebellar ataxia type 3 SG stress granule sHSP small heat shock protein SMA spinal muscular atrophy SMN protein survival-of-motor-neurons protein SOD1 Zn-superoxide dismutase-1 SWOP second window of ischemic preconditioning TAK-1 TGF-beta-activated kinase1 TG transgenic TGF transforming growth factor TLR4 Toll-like receptor 4 VCP valosin-containing protein WM white matter WT wild type HSPB8 Chaperon activity BAG-3 Autophagy Mutation |
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