Molecular chaperone that promotes the maturation, structuralmaintenance and proper regulation of specific target proteins involvedfor instance in cell cycle control and signal transduction. Undergoes afunctional cycle that is linked to its ATPase activity which isessential for its chaperone activity. This cycle probably inducesconformational changes in the client proteins, thereby causing theiractivation. Interacts dynamically with various co-chaperones thatmodulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of clientprotein classes via its interaction with various co-chaperone proteinsor complexes, that act as adapters, simultaneously able to interactwith the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed byclient protein forms a functional chaperone. After the completion ofthe chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation andfinally, ADP is released from HSP90 which acquires an open conformationfor the next cycle. Plays a criticalrole in mitochondrial import, delivers preproteins to the mitochondrialimport receptor TOMM70. Apart from its chaperoneactivity, it also plays a role in the regulation of the transcriptionmachinery. HSP90 and its co-chaperones modulate transcription at leastat three different levels. In the first place, theyalter the steady-state levels of certain transcription factors inresponse to various physiological cues. Second, theymodulate the activity of certain epigenetic modifiers, such as histonedeacetylases or DNA methyl transferases, and thereby respond to thechange in the environment. Third, they participate inthe eviction of histones from the promoter region of certain genes andthereby turn on gene expression. Binds bacteriallipopolysaccharide (LPS) and mediates LPS-induced inflammatoryresponse, including TNF secretion by monocytes. Antagonizes STUB1-mediated inhibition of TGF-beta signaling viainhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Mediates the association of TOMM70 with IRF3 or TBK1in mitochondrial outer membrane which promotes host antiviral response. [1-4]

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