What is the function of Hsp90?
Hsp90 is a highly abundant and ubiquitous molecular chaperone which plays an essential role in many cellular processes including cell cycle control, cell survival, hormone and other signalling pathways. It is important for the cell’s response to stress and is a key player in maintaining cellular homeostasis.
Why is Hsp90 important for receptors?
Hsp90 stabilizes various growth factor receptors and some signaling molecules including PI3K and AKT proteins. Hence inhibition of Hsp90 downregulates the PI3K/AKT pathway leading to downregulation of the anti-apoptotic protein Bcl-w resulting in apoptosis of cancerous and senescent cells.
How do Hsp90 inhibitors work?
Natural product inhibitors HSP90 has conserved unique pocket in N terminal region. It binds ATP & ADP and has weak ATPase activity. Geldanamycin and radicicol tightly bind to this pocket and prevent the release of protein from chaperone complex.
What is the importance of protein protein Interaction?
Protein-protein interactions (PPIs) play a crucial role in cellular functions and biological processes in all organisms. The identification of protein interactions can lead to a better understanding of infection mechanisms and the development of several medication drugs and treatment optimization.
How is Hsp90 activated?
Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters.
What is a client protein?
A term of art for a protein which is manipulated or processed, as in the folding of a client protein by a chaperone.
Is Hsp90 a dimer?
At physiological concentration, Hsp90 predominantly forms dimers, but the function of full-length monomers in cells is not clear. Hsp90 contains three domains: the N-terminal and middle domains contribute directly to ATP binding and hydrolysis and the C domain mediates dimerization.
How hot should heat shock proteins be?
For instance, fruit flies, normally grown at 25 °C in the laboratory, are heat shocked at 35–37 °C, whereas human or mouse cells are induced to make Hsps when the temperature is raised to several degrees above their normal body temperature of 37 °C, for instance 41–42 °C.
How does protein-protein interaction work?
Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and the hydrophobic effect.
What is the role of heat shock protein 90 Hsp90 in the cell?
Purpose of review: Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of a number of conditionally activated and/or expressed signaling proteins, as well as multiple mutated, chimeric, or overexpressed signaling proteins, which promote cancer cell growth or survival or both.
Is Hsp90 a transcription factor?
Hsp90 governs the transcription factor network controlling chromatin status. Hsp90 mediates a late folding step required for transcription factor DNA-binding activity. Hsp90 supports the steady-state stability of transcription factor proteins.