What is HSP90AA1 Protein
Heat shock protein 90 alpha family class A member 1 (HSP90AA1) is a ubiquitous molecular chaperone that plays a central role in maintaining cellular homeostasis.
HSP90AA1 is an evolutionarily conserved member of the heat shock protein family and is a ubiquitous molecular chaperone in eukaryotic cells. The core feature of HSP90AA1 is a tridomain structure: an N-terminal domain, responsible for ATP binding and hydrolysis; a middle domain, essential for interaction with co-chaperones and client proteins; and a C-terminal domain, promoting dimerization for the formation of the functional HSP90AA1 homodimer.
The Function of HSP90AA1 Protein
The primary function of HSP90AA1 revolves around protein folding and stabilization. As a molecular chaperone, HSP90AA1 contributes to the correct folding and stabilization of multiple client proteins, including kinases, transcription factors, and signaling molecules. The chaperone cycle involves ATP binding and hydrolysis, resulting in conformational changes necessary for efficient client protein folding.
In addition to its role in protein folding, HSP90AA1 actively regulates cell signaling pathways. It regulates the PI3K/AKT/mTOR pathway, affecting cell growth and survival. Furthermore, HSP90AA1 plays a key role in the MAPK/ERK pathway and is essential for cell proliferation and differentiation. This chaperone also affects the NF-κB signaling pathway, helping to regulate immune and inflammatory responses.
In response to environmental stress, HSP90AA1 is upregulated, suggesting its role in cellular adaptive responses. This dynamic chaperone function extends to the regulation of cellular processes such as differentiation, proliferation, and survival, making HSP90AA1 critical for cellular homeostasis.
HSP90AA1-Related Diseases
Dysregulation of HSP90AA1 has been implicated in a variety of diseases, emphasizing its importance as a potential therapeutic target or diagnostic marker.
- Cancer
In the world of cancer research, HSP90AA1 has emerged as a key player. Cancer cells exploit the chaperone function of HSP90AA1 to stabilize oncoproteins and promote uncontrolled cell growth. HSP90AA1 inhibitors destabilize oncoproteins, providing a promising avenue for cancer treatment. Ongoing clinical trials are investigating the efficacy of HSP90 inhibitors in a variety of cancers, highlighting the potential of HSP90AA1 as a precision cancer therapeutic target.
- Neurodegenerative Diseases
HSP90AA1's association with neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, has made it a focus of disease research. HSP90AA1 may cause protein misfolding and aggregation, key phenomena associated with neuronal damage. Studying HSP90AA1 in the context of neurodegenerative diseases could provide insights into disease mechanisms and potential therapeutic interventions.
- Cardiovascular Diseases
The association of HSP90AA1 with cardiovascular diseases such as heart failure and atherosclerosis highlights its role in maintaining the stability and activity of proteins critical for cardiac function and vascular homeostasis. Exploring the complex link between HSP90AA1 and cardiovascular disease opens avenues for targeted interventions in cardiovascular medicine.
Figure 1. Proposed model of the mechanism of HSP90AA1 gene in osteosarcoma drug resistance (Xiao, X., et al. 2018)HSP90AA1 Related Signaling Pathways
HSP90AA1's effects on cell signaling pathways add a layer of complexity to its role in cellular regulation.
- PI3K/AKT/mTOR Pathway
HSP90AA1 regulates the PI3K/AKT/mTOR pathway, a core signaling cascade for cell growth and survival. By stabilizing proteins in this pathway, HSP90AA1 contributes to cellular responses to growth factors and environmental signals, thereby affecting a variety of cellular processes.
- MAPK/ERK Pathway
The MAPK/ERK pathway is critical for cell proliferation and differentiation and is complexly regulated by HSP90AA1. The chaperone function of HSP90AA1 is critical for maintaining the stability and activity of kinases within this pathway, highlighting its role in cellular homeostasis.
- NF-κB Signaling
The effects of HSP90AA1 extend to the NF-κB signaling pathway, a core regulator of immune and inflammatory responses. Stabilization of key proteins in this pathway by HSP90AA1 helps regulate immune and inflammatory processes, providing potential therapeutic implications for inflammatory diseases.
Applications of HSP90AA1 in Biomedical Research
The multifunctional role of HSP90AA1 in cellular processes makes it a valuable asset in biomedical research, with applications ranging from cancer therapy to diagnostic markers.
- Target for Cancer Therapy
The central role of HSP90AA1 in cancer cell survival makes it an attractive target for cancer therapy. HSP90 inhibitors are designed to disrupt the stability of oncoproteins and hold promise as precision cancer therapeutics. Ongoing clinical trials aim to validate the efficacy of HSP90 inhibitors in various cancers, paving the way for targeted and personalized cancer treatments.
- Diagnostic and Prognostic Marker
The deregulation of HSP90AA1 in disease, especially cancer, makes it a potential diagnostic and prognostic marker. Monitoring HSP90AA1 levels in biological samples provides a non-invasive method for early disease diagnosis and prognostic assessment, helping to improve patient outcomes.
- Neurodegenerative Disease Research
In the field of neurodegenerative diseases, HSP90AA1 is a focus for understanding disease mechanisms. Studying its role in protein misfolding and aggregation provides important insights that could guide the development of targeted therapies for Alzheimer's and Parkinson's diseases.
The significance of HSP90AA1 spans from the microscopic realm of protein folding to the macroscopic realm of disease and biomedical applications. The journey to unraveling the mystery of HSP90AA1 is an exciting frontier in biological research, promising transformative breakthroughs with far-reaching impacts on human health.
Recommended Products for HSP90AA1 Protein
| Cat.# | Species | Product name | Source (Host) | Tag |
|---|---|---|---|---|
| HSP90AA1-70H | Human | Active Recombinant Human HSP90AA1 | E.coli | N/A |
| HSP90AA1-136H | Human | Recombinant Human HSP90AA1 protein, MYC/DDK-tagged | HEK293 | Myc/DDK |
| HSP90AA1-318H | Human | Recombinant Human Heat Shock Protein 90kDa Alpha (Cytosolic), Class A Member 1 | E.coli | His |
| HSP90AA1-3097H | Human | Recombinant Human HSP90AA1, None tagged | E.coli | N/A |
| HSP90AA1-135H | Human | Recombinant Human Heat Shock Protein 90kDa Alpha (cytosolic), Class A Member 1, His-tagged | E.coli | His |
| Hsp90aa1-32M | Mouse | Recombinant Mouse Hsp90aa1 protein, His-tagged | E.coli | His |
| HSP90AA1-4349M | Mouse | Recombinant Mouse HSP90AA1 Protein, His (Fc)-Avi-tagged | HEK293 | His (Fc)-Avi |
| HSP90AA1-2939R | Rat | Recombinant Rat HSP90AA1 Protein | Mammalian Cell | His |
| HSP90AA1-604C | Cynomolgus Monkey | Recombinant Cynomolgus HSP90AA1 Protein, His-tagged | Mammalian Cell | His |
| HSP90AA1-3762C | Chicken | Recombinant Chicken HSP90AA1 | Mammalian Cell | His |
Reference
- Xiao, X., et al. HSP90AA1-mediated autophagy promotes drug resistance in osteosarcoma. J Exp Clin Cancer Res. 2018, 37: 201.
