Heat Shock Protein HSPA8: A Potential Drug Target and Biomarker

Target Name: HSPA8

NCBI ID: G3312

HSPA8

Heat Shock Protein HSPA8: A Potential Drug Target and Biomarker

Heat shock cognate protein (HSPA8), a 71-kDa protein, has been identified as a potential drug target and biomarker for various diseases, including neurodegenerative disorders, cancer, and autoimmune diseases. Its functions in regulating cellular stress responses and DNA damage have also led to its potential as a therapeutic agent.

HSPA8 is a heat-induced protein that is expressed in various tissues, including brain, heart, liver, and muscle. Its protein level increases in response to heat stress, such as exercise or exposure to UV radiation, and its levels decrease as stress resolves. This increase in HSPA8 protein has been linked to cellular stress and DNA damage, which can lead to the development of various diseases.

One of the known functions of HSPA8 is its role in the regulation of DNA damage. DNA damage, caused by various factors such as ionizing radiation, UV radiation, and metabolic stress, can lead to the formation of reactive oxygen species (ROS), which can cause cellular stress and contribute to the development of various diseases. HSPA8 has been shown to protect against ROS-induced cellular stress by regulating the expression of genes involved in DNA damage repair and stress signaling pathways.

HSPA8 has also been shown to play a role in the regulation of neurodegenerative disorders. neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease are characterized by the progressive loss of brain cells and the development of various cognitive and motor impairments. HSPA8 has been linked to the regulation of neurodegenerative disorder-related genes, including those involved in neurotransmitter synthesis, neuroprotective signaling pathways, and stress signaling pathways.

In addition to its potential role in neurodegenerative disorders, HSPA8 has also been shown to be involved in the regulation of cancer development. Cancer is characterized by the rapid and uncontrolled growth of cells, which can be caused by various factors including genetic mutations, UV radiation, and metabolic stress. HSPA8 has been shown to be involved in the regulation of cell cycle progression and the production of mitochondrial ROS, which are known to contribute to the development of cancer.

Furthermore, HSPA8 has also been shown to be involved in the regulation of autoimmune diseases. Autoimmune diseases are characterized by the immune system attacking the body's own tissues, leading to the development of various diseases such as rheumatoid arthritis, lupus, and multiple sclerosis. HSPA8 has been shown to be involved in the regulation of immune cell function and the production of autoantibodies, which are known to contribute to the development of autoimmune diseases.

In conclusion, HSPA8 is a protein that has been identified as a potential drug target and biomarker for various diseases. Its functions in regulating cellular stress responses and DNA damage have also led to its potential as a therapeutic agent. Further research is needed to fully understand the role of HSPA8 in the development and progression of various diseases.

Protein Name: Heat Shock Protein Family A (Hsp70) Member 8

Functions: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:2799391, PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24318877, PubMed:27474739, PubMed:24121476, PubMed:26865365). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:2799391, PubMed:11559757, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:2799391, PubMed:11559757, PubMed:36586411). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). Interacts with VGF-derived peptide TLQP-21 (PubMed:28934328)

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•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
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•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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