Dominant-negative <i>TP53</i> mutations potentiated by the HSF1-regulated proteostasis network.

ABSTRACT: Protein mutational landscapes are sculpted by the impacts of the resulting amino acid substitutions on the protein's stability and folding or aggregation kinetics. These properties can, in turn, be modulated by the composition and activities of the cellular proteostasis network. Heat shock factor 1 (HSF1) is the master regulator of the cytosolic and nuclear proteostasis networks, dynamically tuning the expression of cytosolic and nuclear chaperones and quality control factors to meet demand. Chronic increases in HSF1 levels and activity are prominent hallmarks of cancer cells. One plausible explanation for this observation is that the consequent upregulation of proteostasis factors could biophysically facilitate the acquisition of oncogenic mutations. Here, we experimentally evaluate the i

SUBMITTER: Sebastian RM 

PROVIDER: S-EPMC11565964 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature