HSPA8

Fig1. The role of HSC70 in MHC class II antigen trafficking and presentation. (Sarah N Deffit, 2015)

What is HSPA8 protein?

HSPA8 (heat shock protein family A (Hsp70) member 8) gene is a protein coding gene which situated on the long arm of chromosome 11 at locus 11q24. HSPA8, also known as HSC70, belongs to the heat shock protein 70 family which contains both heat-inducible and constitutively expressed members. The latter are called heat-shock cognate proteins. This protein is a heat-shock cognate protein. HSPA8 binds to nascent polypeptides to facilitate correct folding. The HSPA8 protein is consisted of 646 amino acids and its molecular mass is approximately 70.9 kDa.

What is the function of HSPA8 protein?

The HSPA8 protein is a versatile molecular chaperone whose main function is to help other proteins fold, assemble, locate, and degrade properly. It is one of the key factors in cells' response to environmental stress (such as high temperature, oxidative stress, etc.) and protects cells from damage by maintaining protein homeostasis. HSPA8 is also involved in regulating cell signaling and immune responses, maintaining cell health by recognizing misfolded or damaged proteins and promoting their repair or removal.

HSPA8 Related Signaling Pathway

When cells are subjected to external stimuli (such as heat shock, oxidative stress, drugs, etc.) leading to abnormal folding and aggregation of proteins, HSPA8 is activated and participates in the refolding and aggregation of misfolded proteins. HSPA8 is associated with autophagy protein, which is involved in regulating the process of autophagy. HSPA8 is involved in the regulation of various signaling pathways, affecting cell survival and apoptosis, cell proliferation and differentiation, such as the Wnt/β-Catenin signaling pathway.

HSPA8 Related Diseases

HSPA8 expression was up-regulated in a variety of cancers, including colorectal cancer, breast cancer, and gastric cancer. It is involved in the genesis and development of tumors by regulating cell proliferation, apoptosis and autophagy. It is upregulated in neurodegenerative diseases such as Alzheimer's and Parkinson's, and plays a role in some cardiovascular and inflammatory diseases.

Bioapplications of HSPA8

Detection of HSPA8 levels in the body can help diagnose, monitor disease progression, and evaluate treatment effects. Because of its role in tumorigenesis and progression, HSPA8 is considered a potential therapeutic target.

Case study 1: Lei Wang, 2022

Porcine reproductive and respiratory syndrome virus (PRRSV), a porcine arterivirus, causes severe financial losses to global swine industry. Despite much research, the molecular mechanisms of PRRSV infection remains to be fully elucidated.

In this study, the researchers uncovered the involvement of heat shock protein member 8 (HSPA8) in PRRSV attachment and internalization during infection for the first time. In detail, HSPA8 was identified to interact with PRRSV glycoprotein 4 (GP4). Chemical inhibitors and specific small interference RNAs (siRNAs) targeting HSPA8 significantly suppressed PRRSV infection as indicated by decreased viral RNA abundance, infectivity, and titers. these results demonstrate that HSPA8 is important for PRRSV attachment and internalization, which is a potential target to prevent and control the viral infection.

Fig1. GP4-mCherry co-localized with endogenous HSPA8. HEK-293T cells were transfected with the plasmid expressing GP4-mCherry (red) or mCherry (red) for 24 h, and stained with anti-HSPA8 pAbs.

Fig2. HSPA8 PB domain interacted with GP4-mCherry.

Case study 2: Riccardo Sirtori, 2020

Heat shock protein 70 family was demonstrated to play a critical role in protein homeostasis, a process profoundly impaired in neurodegenerative disorders. Neurodegenerative diseases are characterized by the accumulation of different kind of proteins and the formation of insoluble aggregates which are toxic for neurons. To explore the role of heat shock protein family 70 (in particular HSPA8 and HSPA1A) in the accumulation of proteins implied in neurodegeneration pathogenesis, in this study the researchers verified in human SH-SY5Y neuroblastoma cells how HSPA8 or HSPA1A knock-down can affect protein levels of tau, superoxide dismutase 1 and α-synuclein. The results suggest HSPA8 can play an important role in the homeostasis of tau, superoxide dismutase 1 and α-synuclein and in the balance between α-synuclein oligomeric and monomeric forms.

Fig3. siRNA-mediated knock-down of HSPA8 and HSPA1A in SH-SY5Y cell line. Relative protein levels of HSPA8 and HSPA1A after silencing of HSPA8 or HSPA1A.

Fig4. Representative Western blot images in SH-SY5Y knocked-down for HSPA8 or HSPA1A.

HSPA8 has several biochemical functions, for example, ATP binding,ATPase activity,ATPase activity, coupled. Some of the functions are cooperated with other proteins, some of the functions could acted by HSPA8 itself. We selected most functions HSPA8 had, and list some proteins which have the same functions with HSPA8. You can find most of the proteins on our site.

HSPA8 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with HSPA8 here. Most of them are supplied by our site. Hope this information will be useful for your research of HSPA8.

STUB1;LRRK2;HSPBP1;EGFR