The SIRT1 modulators AROS and DBC1 regulate HSF1 activity and the heat shock response.
The heat shock response, the cellular response to protein damaging stress, is critical in maintaining proteostasis. The heat shock response is regulated by the transcription factor HSF1, which is activated upon heat shock and other stresses to induce the expression of molecular chaperones. SIRT1 has previously been shown to activate HSF1 by deacetylating it, leading to increased DNA binding ability. We have investigated how the heat shock response may be controlled by factors influencing SIRT1 activity. We found that heat shock results in an increase in the cellular NAD(+)/NADH ratio and an increase in recruitment of SIRT1 to the hsp70 promoter. Furthermore, we found that the SIRT1 modulators AROS and DBC1 have an impact on hsp70 transcription, HSF1 acetylation status, and HSF1 recruitment to the hsp70 promoter. Therefore, AROS and DBC1 are now two new targets available for therapeutic regulation of the heat shock response.
The Department of Cell Biology, Microbiology and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, Florida, USA.
Rachel
R
Raynes
Kathleen M
KM
Pombier
Kevin
K
Nguyen
Jessica
J
Brunquell
Jamie E
JE
Mendez
Sandy D
SD
Westerheide
D000107:Acetylation; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D006358:Hot Temperature; D006801:Humans; D009243:NAD / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C112308:BRINP1 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C524448:RPS19BP1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D009243:NAD; C447939:SIRT1 protein, human; D056564:Sirtuin 1