Maria Skłodowska-Curie Institute - Oncology Center, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101, Gliwice, Poland.
Cell Oncol (Dordr). 2019 Oct;42(5):579-589. doi: 10.1007/s13402-019-00452-0. Epub 2019 Jun 10.
The p53 and HSF1 transcription factors are key players in cellular responses to stress. They activate important signaling pathways triggering adaptive mechanisms that maintain cellular homeostasis. HSF1 is mainly activated by proteotoxic stress, and its induction leads to the synthesis of chaperones that provide proteome integrity. The p53 protein, which is primarily activated in response to DNA damage, causes cell cycle arrest allowing for DNA repair or directs cells to apoptosis, thereby maintaining genome integrity. Both signaling pathways are also involved in neoplastic transformation and tumor progression. Loss of tumor suppressor abilities of the wild-type p53 protein results in oncogenesis, whereas proper HSF1 action, though non-oncogenic itself, actively supports this process.
Here, we describe in detail the interplay between the p53 and HSF1 signaling pathways, with particular emphasis on the molecular mechanisms involved, as well as their importance for normal cellular behavior, cancer development, the effectiveness of anti-cancer therapies and their toxicity. Detailed knowledge of the complex interplay between HSF1 and p53 may form a basis for the design of new protocols for cancer treatment.
p53 和 HSF1 转录因子是细胞应激反应的关键因素。它们激活重要的信号通路，触发适应性机制，维持细胞内稳态。HSF1 主要被蛋白毒性应激激活，其诱导导致伴侣蛋白的合成，提供蛋白质组的完整性。p53 蛋白主要在响应 DNA 损伤时被激活，导致细胞周期停滞，从而允许 DNA 修复或指导细胞凋亡，从而维持基因组的完整性。这两个信号通路也参与了肿瘤的转化和进展。野生型 p53 蛋白肿瘤抑制能力的丧失导致了癌变，而适当的 HSF1 作用本身虽然非致癌，但却积极地支持这一过程。
在这里，我们详细描述了 p53 和 HSF1 信号通路之间的相互作用，特别强调了所涉及的分子机制，以及它们对正常细胞行为、癌症发展、抗癌治疗的效果及其毒性的重要性。详细了解 HSF1 和 p53 之间的复杂相互作用可能为设计新的癌症治疗方案奠定基础。
