Agnieszka Toma-Jonik1, Natalia Vydra1, Patryk Janus1, Wiesława Widłak2. 1. Maria Skłodowska-Curie Institute - Oncology Center, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101, Gliwice, Poland. 2. Maria Skłodowska-Curie Institute - Oncology Center, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101, Gliwice, Poland. wieslawa.widlak@io.gliwice.pl.
Abstract
BACKGROUND: 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. CONCLUSIONS: 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.
BACKGROUND: 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. CONCLUSIONS: 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.
Authors: Anna Paszek; Małgorzata Kardyńska; James Bagnall; Jarosław Śmieja; David G Spiller; Piotr Widłak; Marek Kimmel; Wieslawa Widlak; Pawel Paszek Journal: Cell Commun Signal Date: 2020-05-24 Impact factor: 5.712
Authors: Qianze Dong; Yan Xiu; Yang Wang; Christina Hodgson; Nick Borcherding; Craig Jordan; Jane Buchanan; Eric Taylor; Brett Wagner; Mariah Leidinger; Carol Holman; Dennis J Thiele; Sean O'Brien; Hai-Hui Xue; Jinming Zhao; Qingchang Li; Howard Meyerson; Brendan F Boyce; Chen Zhao Journal: Nat Commun Date: 2022-10-16 Impact factor: 17.694
Authors: Margot De Marco; Antonia Falco; Roberta Iaccarino; Antonio Raffone; Antonio Mollo; Maurizio Guida; Alessandra Rosati; Massimiliano Chetta; Giovanni Genovese; Francesco De Caro; Mario Capunzo; Maria Caterina Turco; Vladimir N Uversky; Liberato Marzullo Journal: Br J Cancer Date: 2021-06-07 Impact factor: 9.075