I-BOP

Overview

Hsp70, or Heat Shock Protein 70, is a family of highly conserved proteins that play a critical role in protein folding, protection of cells from stress, and the regulation of the heat shock response. These proteins are found in virtually all living organisms, from bacteria to humans, and are essential for cellular homeostasis.

Structure

Hsp70 proteins are characterized by their molecular weight of approximately 70 kDa. They consist of two main domains:

• The N-terminal ATPase domain, which binds and hydrolyzes ATP, providing the energy required for the protein's chaperone activity.
• The C-terminal substrate-binding domain, which interacts with unfolded or misfolded polypeptides, preventing their aggregation and assisting in their proper folding.

Function

Hsp70 proteins function as molecular chaperones, assisting in the folding of nascent polypeptides, the refolding of misfolded proteins, and the translocation of proteins across cellular membranes. They are also involved in the degradation of proteins via the ubiquitin-proteasome pathway.

Stress Response

Under conditions of stress, such as heat shock, oxidative stress, or exposure to toxins, the expression of Hsp70 is upregulated. This response is mediated by heat shock factors (HSFs), which bind to heat shock elements (HSEs) in the promoter regions of Hsp70 genes, enhancing their transcription.

Role in Disease

Hsp70 has been implicated in various diseases, including cancer, neurodegenerative disorders, and infectious diseases. In cancer, Hsp70 can promote tumor cell survival by inhibiting apoptosis and stabilizing oncoproteins. In neurodegenerative diseases, such as Alzheimer's and Parkinson's, Hsp70 may help in reducing the aggregation of misfolded proteins.

Clinical Applications

Due to its role in protein homeostasis and stress response, Hsp70 is a target for therapeutic interventions. Small molecules that modulate Hsp70 activity are being investigated for their potential to treat cancer and neurodegenerative diseases.

Also see

• Heat shock protein
• Chaperone (protein)
• Protein folding
• Heat shock factor
• Ubiquitin-proteasome pathway