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  • Title: Novel regulatory factors of HSF-1 activation: facts and perspectives regarding their involvement in the age-associated attenuation of the heat shock response.
    Author: Shamovsky I, Gershon D.
    Journal: Mech Ageing Dev; 2004; 125(10-11):767-75. PubMed ID: 15541771.
    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.
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