Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery. Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription. Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10.

1. The results demonstrate that in renal cells, NHE1 is associated with several regulatory proteins including Hsp90, and that Hsp90 affects its function possibly through altered phosphorylation of the protein via the AKT kinase. PMID: 28483634
2. Hsp90 is highly expressed on the cell surface of melanoma cells, and synthetic agents that target Hsp90 are promising cancer therapeutic drugs PMID: 27575453
3. Data show that docetaxel, rapamycin and tanespimycin multi-drug loaded micelles targeted against HSP90 and the PI3K/AKT/mTOR pathway in prostate cancer. PMID: 28350865
4. genes respond to HSP90 inhibition in a manner dependent on their genomic location with regard to strain-specific endogenous retroviruses-insertion sites. PMID: 28134929
5. PABPN1 interacts with and is stabilized by heat shock protein 90. PMID: 26414348
6. These findings demonstrate a critical role of Hsp90 in lipopolysaccharide (LPS) signaling, and a potential involvement of the heat shock response in LPS-induced preconditioning. PMID: 24646925
7. Phosphoproteomics, protein expression inference and signaling pathway prediction analysis of P2RX7 signaling mediators pointed to HSPA2 and HSP90 proteins. PMID: 25700737
8. Hsp90 inhibition plays a key role in preventing the recurrence of HCC, and the combination of ablation with targeted therapy holds great potential to improve prognosis and survival of HCC patients. PMID: 25403416
9. These findings demonstrate CKII induces polymerization of soluble TDP-43 into filaments and Hsp90 promotes TDP-43 filament depolymerization. PMID: 24595055
10. Reveal an opposite role of Hsp70 and Hsp90 in regulating TGF-beta signaling by implicating CHIP-mediated Smad3 ubiquitination and degradation. This study provides a new insight into understanding the regulation of the TGF-beta signaling by chaperones. PMID: 24613385
11. A novel role for Hsp90 in controlling PPARgamma stability and cellular differentiation, is reported. PMID: 24096869
12. inhibition exerts an anti-inflammatory effect in murine models of colitis PMID: 23321985
13. Hsp90 activity is necessary to control the expression, activity or location of specific kinases and motor proteins during the axon specification and axon elongation processes. PMID: 24286867
14. Alcohol-induced cilia stimulation occurs through the increased association of HSP90 with miR-122 target gene endothelial nitric oxide synthase (eNOS). PMID: 23078267
15. Results suggest that heat shock protein 90 inhibitor radicicol inhibited 3T3-L1 preadipocyte differentiation through affecting the PDK1/Akt pathway. PMID: 23727383
16. Perturbation of the HSP70-HSP90 heat-shock protein axis stimulates degradation of endothelial VEGFR2. PMID: 23139789
17. Hsp90 expression is up-regulated in injured arteries and colocalizes with the apoptosis inhibitor, survivin, in vascular smooth muscle cell in vitro and in vivo. PMID: 22841823
18. HSP90 is expressed in the vast majority of pancreatic endocrine tumors and inhibition of HSP90 results in a significant reduction of cell viability, cell cycle arrest, and increased apoptosis PMID: 22194440
19. HSP90 may modulate myogenic differentiation and may be involved in cell survival. PMID: 21739150
20. This study concluded that hsp90 plays a primary role in maturation of iNOS protein by interacting with the apoenzyme in cells and then driving heme insertion in an ATP-dependent manner. PMID: 21357526
21. involved in translocation of a chaperoned antigen from endosome to proteasome for cross-presentation by dendritic cells PMID: 21421737
22. The beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein heat shock protein 90. Inhibition of HSP90 enhances the suppressive functions of Foxp3+ Tregs. PMID: 21444725
23. This results in the transcriptional repression of Hsp90beta, under GSH-deficient conditions which may play a role in arsenic-mediated pathogenesis. PMID: 18996350
24. Heat shock protein 84 from C57BL/6 mice modulates higher cellular glucocorticoid-glucocorticoid receptor responsiveness. PMID: 20332616
25. This study is the first report identifying four genetic variations of the murine hsp84 gene: 226A>C, 996G>C, 1483G>C, and 2000G>T. PMID: 19845467
26. Data show that inhibition of Hsp90 engages a p53-dependent pathway to apoptosis. PMID: 19805107
27. Hsp90 binding to Galpha12 helps target Galpha12 to lipid rafts PMID: 12117999
28. peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein PMID: 12482853
29. mineralocorticoid receptor and HSP84 mediate Src activation by aldosterone PMID: 15251441
30. in the cytoplasm linker histones are bound to a complex containing NASP and HSP90 whose ATPase activity is stimulated by binding NASP PMID: 15533935
31. The antiapoptotic activity of Bcl-2 was greatly affected by knocking-out specifically Hsp90beta using the RNA interference approach. PMID: 16166581
32. Hsp90beta is distinct from Hsp90alpha in regulation of the cellular function of immune cells. PMID: 17475835
33. A possible role of Hsp84 in mouse suprachiasmatic nucleus is association with circadian rhythms. PMID: 18480550
34. These data provide an explanation for apoptosome inhibition by activated leukemogenic tyrosine kinases and suggest that alterations in Hsp90beta-apoptosome interactions may contribute to chemoresistance in leukemias. PMID: 18591256
35. analyzed meiotic maturation in wild-type oocytes treated with a specific inhibitor of Hsp90, 17-allylamino-17-demethoxy-geldanamycin, and observed similar defects PMID: 19158073
36. Findings suggest that Hsp90 inhibitors might represent a novel means of promoting T cell tolerance. PMID: 19586661

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Cytoplasm. Melanosome. Nucleus. Secreted. Cell membrane. Dynein axonemal particle.

Heat shock protein 90 family

KEGG: mmu:15516

STRING: 10090.ENSMUSP00000024739

UniGene: Mm.2180