Novel regulatory factors of HSF-1 activation: facts and perspectives regarding their involvement in the age-associated attenuation of the heat shock response.
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.
Shamovsky
Ilya
I
Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Gershon
David
D
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D000076249:Heat Shock Transcription Factors; D018882:Heat Stress Disorders / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D020648:Peptide Elongation Factor 1 / Q000378:metabolism*; D015138:RNA, Nuclear / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D020648:Peptide Elongation Factor 1; D015138:RNA, Nuclear; D014157:Transcription Factors