PMID- 15541771 OWN - NLM STAT- MEDLINE DCOM- 20050520 LR - 20171116 IS - 0047-6374 (Print) IS - 0047-6374 (Linking) VI - 125 IP - 10-11 DP - 2004 Oct-Nov TI - Novel regulatory factors of HSF-1 activation: facts and perspectives regarding their involvement in the age-associated attenuation of the heat shock response. PG - 767-75 AB - 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. FAU - Shamovsky, Ilya AU - Shamovsky I AD - Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. FAU - Gershon, David AU - Gershon D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Mech Ageing Dev JT - Mechanisms of ageing and development JID - 0347227 RN - 0 (DNA-Binding Proteins) RN - 0 (Heat Shock Transcription Factors) RN - 0 (Heat-Shock Proteins) RN - 0 (Peptide Elongation Factor 1) RN - 0 (RNA, Nuclear) RN - 0 (Transcription Factors) SB - IM MH - Aging/*metabolism MH - Animals MH - Brain/metabolism MH - DNA-Binding Proteins/antagonists & inhibitors/*metabolism MH - Female MH - Gene Expression Regulation/*physiology MH - Heat Shock Transcription Factors MH - Heat Stress Disorders/*metabolism MH - Heat-Shock Proteins/biosynthesis MH - Peptide Elongation Factor 1/*metabolism MH - RNA, Nuclear/*metabolism MH - Rats MH - Rats, Wistar MH - Transcription Factors EDAT- 2004/11/16 09:00 MHDA- 2005/05/21 09:00 CRDT- 2004/11/16 09:00 PHST- 2004/11/16 09:00 [pubmed] PHST- 2005/05/21 09:00 [medline] PHST- 2004/11/16 09:00 [entrez] AID - S0047-6374(04)00167-8 [pii] AID - 10.1016/j.mad.2004.07.006 [doi] PST - ppublish SO - Mech Ageing Dev. 2004 Oct-Nov;125(10-11):767-75. doi: 10.1016/j.mad.2004.07.006.