The heat shock response (HSR) was originally discovered as a transcriptional response to elevated temperature shock and led to the identification of heat shock proteins and heat shock factor 1 (HSF1). Since then HSF1 has been shown to be important for combating other forms of environmental perturbations as well as genetic variations that cause proteotoxic stress. The HSR has long been thought to be an absolute response to conditions of cell stress and the primary mechanism by which HSF1 promotes organismal health by preventing protein aggregation and subsequent proteome imbalance. Accumulating evidence now shows that HSF1, the central player in the HSR, is regulated according to specific cellular requirements through cell-autonomous and non-autonomous signals, and directs transcriptional programs distinct from the HSR during development and in carcinogenesis. We discuss here these ‘non-canonical’ roles of HSF1, its regulation in diverse conditions of development, reproduction, metabolism, and aging, and posit that HSF1 serves to integrate diverse biological and pathological responses.

热休克反应（HSR）最初是作为对高温休克的转录反应而发现的，并导致了热休克蛋白和热休克因子1（HSF1）的鉴定。从那以后，HSF1已被证明对抵抗其他形式的环境扰动以及引起蛋白毒性应激的遗传变异具有重要意义。长期以来，人们一直认为HSR是对细胞应激条件的绝对反应，而HSF1通过阻止蛋白质聚集和随后的蛋白质组失衡而促进机体健康，是其主要机制。现在越来越多的证据表明，HSR的核心参与者HSF1通过细胞自主和非自主信号根据特定的细胞需求进行调节，并在发育和致癌过程中指导不同于HSR的转录程序。我们在这里讨论HSF1的这些“非经典”作用，其在发育，繁殖，代谢和衰老的各种条件下的调节，并假定HSF1可以整合各种生物学和病理学反应。