Novel regulatory factors of HSF-1 activation: facts and perspectives regarding their involvement in the age-associated attenuation of the heat shock response.

Abstract

An attenuated response to stress is characteristic of senescence. Heat shock (HS), a significant form of stress, is delayed and reduced in aging organisms. In the response to heat shock, heat shock factor 1 (HSF-1) is activated by trimerization of its monomeric subunits. This then initiates the transcription of a series of heat shock genes (hsp genes) that encode chaperone proteins protective against heat stress. Using a promoter binding electromobility shift assay (EMSA), we have found no activation of this transcription factor in the brains of old (36 months) rats in response to exposure to 41 degrees C for 1h while strong activation is elicited in young (6 months) animals. Since brains of young and old rats had approximately the same amount of HSF-1 subunits, we anticipated the presence of auxiliary regulatory factors essential for the activation of HSF-1 and the initiation of heat shock gene transcription. We describe three novel auxiliary factors--the proteins I-HSF [HSF inhibitor] and elongation factor-1 alpha (EF-1alpha) and a large non-coding RNA (HSR)--that participate in regulation and activation of HSF-1 in early stages of heat shock gene transcription. I-HSF inhibits trimerization of HSF-1 at normal temperatures. HSR and EF-1alpha form a complex with HSF-1 and facilitate its trimerization and binding to heat shock element (HSE) in the promoters of hsps. It is proposed that structural changes in any one or a combination of these factors in response to heat shock may contribute to the age-associated attenuation in the response to stress.

• Authors: Ilya Shamovsky, David Gershon
• Journal: Mechanisms of ageing and development (Mech Ageing Dev) Vol. 125 Issue 10-11 Pg. 767-75 ( 2004) ISSN: 0047-6374 [Print] Ireland
• PMID: 15541771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Heat Shock Transcription Factors
• Heat-Shock Proteins
• Peptide Elongation Factor 1
• RNA, Nuclear
• Transcription Factors

Topics

• Aging (metabolism)
• Animals
• Brain (metabolism)
• DNA-Binding Proteins (antagonists & inhibitors, metabolism)
• Female
• Gene Expression Regulation (physiology)
• Heat Shock Transcription Factors
• Heat Stress Disorders (metabolism)
• Heat-Shock Proteins (biosynthesis)
• Peptide Elongation Factor 1 (metabolism)
• RNA, Nuclear (metabolism)
• Rats
• Rats, Wistar
• Transcription Factors