p(HGNC:HSF1)
High-throughput screens in yeast and HeLa cells identified HSF1A and F1, respectively, as two small molecules that activate HSF1 independently of HSP90 inhibition (136, 137). PubMed:25784053
Upon increased levels of nonnative proteins, HSF1 is released from its repressive complex, acquires DNA-binding activity through homotrimerization, and rapidly translocates to the nucleus to induce expression of genes encoding molecular chaperones (7, 35). PubMed:25784053
Once stress has been relieved, HSF1 activity is repressed through acetylation and binding to molecular chaperones (34, 36, 37). PubMed:25784053
Upon increased levels of nonnative proteins, HSF1 is released from its repressive complex, acquires DNA-binding activity through homotrimerization, and rapidly translocates to the nucleus to induce expression of genes encoding molecular chaperones (7, 35). PubMed:25784053
HSF1A suppresses toxicity in cell and tissue culture models of HD and SCA-3/MJD and appears to activate HSF1 by impairing the activity of TRiC, a recently discovered negative regulator of HSF1. PubMed:25784053
One strategy is to directly activate HSF1, thereby increasing the expression of multiple molecular chaperones simultaneously. This approach has been traditionally achieved by inhibition of HSP90 with compounds that bind the N-terminal ATP-binding pocket, such as radicicol, geldanamycin, or 17-AAG (64, 132–134). PubMed:25784053
Once stress has been relieved, HSF1 activity is repressed through acetylation and binding to molecular chaperones (34, 36, 37). PubMed:25784053
Constitutive activation of HSF1 is detrimental to cells and increased expression, and activity of HSF1 has been linked to multiple forms of cancer, highlighting the need for appropriate and balanced activation of stress response pathways as and when required throughout life (122). PubMed:25784053
One promising agent is the hydroxylamine deriva- tive arimoclomol, which increases the activity of HSP70 by augmenting transcriptional activity of HSF1 (REF.210) . PubMed:30116051
For exam- ple, small molecules (e.g., geldanamycin) that activate heat shock factor 1, the main transcrip- tional regulator of the cytosolic stress response, increase the effective concentration of cytosolic chaperones and suppress the aggregation of various disease proteins (8, 38, 228–230). PubMed:23746257
HDAC6 activity was also reported to regulate chaperone expression in response to heat shock by deacetylating Hsp90 leading to release and activation of the transcription factor HSF-1 [79]. PubMed:18930136
During elevated stress the chaperones within the repressive HSF1-containing multi-chaperone complexes bind the unfolded proteins and thus the liberated monomeric HSF1s undergo phosphorylation, trimerization and nuclear localization with increased transcriptional activity [109]. PubMed:24563850
During elevated stress the chaperones within the repressive HSF1-containing multi-chaperone complexes bind the unfolded proteins and thus the liberated monomeric HSF1s undergo phosphorylation, trimerization and nuclear localization with increased transcriptional activity [109]. PubMed:24563850
Upon increased levels of nonnative proteins, HSF1 is released from its repressive complex, acquires DNA-binding activity through homotrimerization, and rapidly translocates to the nucleus to induce expression of genes encoding molecular chaperones (7, 35). PubMed:25784053
Upon increased levels of nonnative proteins, HSF1 is released from its repressive complex, acquires DNA-binding activity through homotrimerization, and rapidly translocates to the nucleus to induce expression of genes encoding molecular chaperones (7, 35). PubMed:25784053
Constitutive activation of HSF1 is detrimental to cells and increased expression, and activity of HSF1 has been linked to multiple forms of cancer, highlighting the need for appropriate and balanced activation of stress response pathways as and when required throughout life (122). PubMed:25784053
One promising agent is the hydroxylamine deriva- tive arimoclomol, which increases the activity of HSP70 by augmenting transcriptional activity of HSF1 (REF.210) . PubMed:30116051
The expression of Hsps is regulated by heat shock factor 1 (HSF1), which, under stress conditions, becomes associated with heat shock elements to elevate the transcription of Hsps and other proteins [51]. PubMed:21882945
However, the mechanisms that link HSF1 induction to improved proteostasis are not yet clear PubMed:21882945
Therapeutic approaches to overcome proteostasis deficiencies have largely focused on the activation of HSF1, the heat shock transcription factor responsible for simultaneous upregulation of the expression of multiple molecular chaperones during stress (Calamini et al., 2011; Pierce et al., 2013). PubMed:27491084
For exam- ple, small molecules (e.g., geldanamycin) that activate heat shock factor 1, the main transcrip- tional regulator of the cytosolic stress response, increase the effective concentration of cytosolic chaperones and suppress the aggregation of various disease proteins (8, 38, 228–230). PubMed:23746257
For exam- ple, small molecules (e.g., geldanamycin) that activate heat shock factor 1, the main transcrip- tional regulator of the cytosolic stress response, increase the effective concentration of cytosolic chaperones and suppress the aggregation of various disease proteins (8, 38, 228–230). PubMed:23746257
For exam- ple, small molecules (e.g., geldanamycin) that activate heat shock factor 1, the main transcrip- tional regulator of the cytosolic stress response, increase the effective concentration of cytosolic chaperones and suppress the aggregation of various disease proteins (8, 38, 228–230). PubMed:23746257
HSF1 binds to a consensus heat shock element (HSE) within the promoter regions of HSP genes resulting in the activation of HSPs' gene expression and the control of cellular responses to oxidative and proteotoxic stress [108]. PubMed:24563850
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.