Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases

Article ID	Journal	Published Year	Pages	File Type
8469662	European Journal of Cell Biology	2018	71 Pages	PDF

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

TLR4 Hsp FTD SMN HIF-1α ECM SOD1 SBMA TGF RBP ACD HspB8 DRM VCP IPC GSK CK2 SCA3 Sam68 BAG3 RRE sHSP HCHWA-D C-terminus of Hsc70 interacting protein TAK-1 SWOP PKC-ε iNOS MSA MMP-9 PI3K DPR Aβ RNP I/R MAPK OGD/R ischemic preconditioning amyloid β-peptide Multiple system atrophy spinal muscular atrophy spinal and bulbar muscular atrophy Rheumatoid arthritis Autophagy amyotrophic lateral sclerosis ischemia/reperfusion IDPs Alzheimer disease ALS Huntington disease Parkinson’s disease transforming growth factor Transgenic mutation CASA α-Crystallin domain SMA CNS ribonucleoprotein central nervous system peripheral nervous system hypoxia-inducible factor-1α Rev response element frontotemporal dementia phosphatidylinositol 3′-kinase Extracellular matrix matrix metallopeptidase-9 grey matter white matter BMP Multiple sclerosis Spinocerebellar Ataxia Type 3 wild type Valosin-containing protein Heat shock protein small heat shock protein RNA-binding protein Bone morphogenetic protein Intrinsically disordered proteins Protein kinase mitogen-activated protein kinase CHiP PNS Casein kinase 2 Stress granule glycogen synthase kinase Androgen Receptor estrogen-receptor Toll-like receptor 4