Mechanisms of Activation and Inactivation of HSP70 Synthesis

  • Igor MalyshevEmail author
Part of the SpringerBriefs in Biochemistry and Molecular Biology book series (BRIEFSBIOCHEM, volume 6)


The main participants that regulate HSP70 synthesis are the HSP70 genes and the HSF-1 transcription factor. In a non-stressed cell, HSF-1 exists within the cytoplasm in an inactive monomer state. The inactive state of the HSF-1 monomer is supported by the «HSP90-p23-immunophilin» complex and, possibly, by intramolecular hydrophobic bonds and phosphorylation of specific HSF-1 serine residues. HSP70 and HSP40 participate in the formation of the inhibitory complex. Activation of the HSF-1 transcription factor occurs in two steps. The first step occurs when emerging denatured and/or misfolded proteins induce removal of the negative influence of the «HSP90-p23-immunophylin» complex, trimerization of the HSF-1, and the binding of trimerized HSF-1 to a specific region of the hsp70 promoter, termed the HSE. In the second step, the negative influence of the «HSP90-p23-Fkbp52» complex is abolished and transcription is activated. Inactivation of HSF-1 and cessation of HSP70 synthesis occurs when HSP70 and HSP40 bind to HSF-1, and thus inhibit HSF-1 transcriptional activity. Thus, the system of HSP70 synthesis includes an autoregulation mechanism; the ability of HSP70 to inactivate its own transcription factor.


HSP70 HSE HSF-1 The HSP70 synthesis 


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© The Author(s) 2013

Authors and Affiliations

  1. 1.Department of PathophysiologyMoscow State University of Medicine and dentistryMoscowRussia

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