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Attenuation phase

Reactome ID: R-HSA-3371568

中文名称

衰减阶段

通路描述

热休克转录反应衰减发生在连续暴露于中等热休克条件或从应激恢复期间。HSF1 循环的衰减阶段涉及 HSF1 与 HSE 结合后转录沉默、从 HSE 释放 HSF1 三聚体以及 HSF1 三聚体解离为单体。HSF1 驱动的与热应激相关的转录依赖于 HSF1 在赖氨酸 80 位的可诱导和可逆乙酰化,这负调控 HSF1 的 DNA 结合活性。此外,当足够的 HSP70/HSP40 产生以饱和因热暴露导致的蛋白质暴露的疏水区域时,HSF1 激活的衰减发生。过量的 HSP70/HSP40 与 HSF1 三聚体结合,导致其从启动子解离并转化为无活性的单体形式。HSF70 与转录核心抑制因子 1-沉默转录因子核心抑制复合物(CoREST)的相互作用有助于终止热休克反应。HSF1 结合蛋白(HSBP1)与活性三聚体 HSF1 的相互作用还抑制了 HSF1 的 DNA 结合和转录激活活性。
英文描述
Attenuation phase Attenuation of the heat shock transcriptional response occurs during continuous exposure to intermediate heat shock conditions or upon recovery from stress (Abravaya et al. 1991). The attenuation phase of HSF1 cycle involves the transcriptional silencing of HSF1 bound to HSE, the release of HSF1 trimers from HSE and dissociation of HSF1 trimers to monomers. HSF1-driven heat stress associated transcription was shown to depend on inducible and reversible acetylation of HSF1 at Lys80, which negatively regulates DNA binding activity of HSF1 (Westerheide SD et al. 2009). In addition, the attenuation of HSF1 activation takes place when enough HSP70/HSP40 is produced to saturate exposed hydrophobic regions of proteins damaged as a result of heat exposure. The excess HSP70/HSP40 binds to HSF1 trimer, which leads to its dissociation from the promoter and conversion to the inactive monomeric form (Abravaya et al. 1991; Shi Y et al. 1998). Interaction of HSP70 with the transcriptional corepressor repressor element 1-silencing transcription factor corepressor (CoREST) assists in terminating heat-shock response (Gomez AV et al. 2008). HSF1 DNA-binding and transactivation activity were also inhibited upon interaction of HSF1-binding protein (HSBP1) with active trimeric HSF1(Satyal SH et al. 1998).

所含基因

13 个基因