What is HSP90 cancer?
The molecular chaperone heat shock protein 90 (HSP90) has been used by cancer cells to facilitate the function of numerous oncoproteins, and it can be argued that cancer cells are ‘addicted’ to HSP90.
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.
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.
Where is HSP90 found?
Two forms, HSP90 alpha and HSP90 beta, are located in the cytoplasm, GRP94 (94-kDa glucose-regulated protein) exists in the ER, and TRAP-1 (tumor necrosis factor receptor-associated protein 1) is present in the mitochondria.
How many heat shock proteins are there?
HSPs are divided into five major families, HSP100, 90, 70, 60, and the small HSP (sHSP)/α-crystallins, according to their molecular weight, structure and function.
What is Hsp100?
Hsp100 chaperones support heat-shock survival of bacteria, yeast, and plants. Hsp100 chaperones (ClpB/Hsp104) belong to the AAA+ family of ATPases. Hsp100 use energy from ATP to extract single polypeptides from aggregated particles.
Are heat shock proteins good or bad?
Heat shock proteins inhibit inflammatory pathways. Heat shock proteins make healthy cells stronger by protecting cells against stress and injuries, making you more resistant to diseases.
What triggers heat shock proteins?
Production of high levels of heat shock proteins can also be triggered by exposure to different kinds of environmental stress conditions, such as infection, inflammation, exercise, exposure of the cell to harmful materials (ethanol, arsenic, and trace metals, among many others), ultraviolet light, starvation, hypoxia ( …
How are Hsp90 inhibitors used to treat cancer?
Both of these emerging aspects of HSP90 biology suggest that the most effective use of HSP90 inhibitors may not be at high doses with the intent to kill cancer cells, but rather in combination with other molecularly targeted therapies at modest, non-heat shock-inducing exposures that limit the adaptive capacity of cancers.
What can be done about the function of Hsp90?
Hsp90 and its co-chaperones are required for the function of these tumor-promoting client proteins; therefore, inhibition of Hsp90 by specific inhibitors such as geldanamycin and its derivatives attenuates the tumor progression.
Is the Hsp90 the chaperone of heat shock?
Several detailed reviews are available that address the molecular and cellular biology of the heat-shock response 5, 6, HSPs in general 7, 8, and HSP90 in particular 1, 9. Despite the name ‘heat-shock’ protein, most chaperones, or their close relatives, are ubiquitously expressed under normal conditions.
Is the heat shock protein 90 an anticancer target?
The stability and function of many oncogenic mutant proteins depend on heat shock protein 90 (HSP90). This unique activity has inspired the exploration of HSP90 as an anticancer target for over two decades.