Fig. 1

Schematic showing the fate of wildtype p53 versus amyloid p53. The cellular consequences due to p53 amyloid formation when compared to wildtype p53 of cells harboring p53 aggregates. Native p53 is a tetrameric transcription factor that regulates several genes by binding to the p53-specific response element (RE) to control the apoptotic, cell cycle arrest, and DNA repair pathways. To maintain cellular homeostasis, native p53 controls cell cycle and proliferation as well. On the other hand, via altering cellular networks primarily involved in the cell cycle, DNA repair, and cell proliferation, amyloid p53 conveys the gain of oncogenic properties to the cells. Amyloid formation causes a significant upregulation of pathways involved in the unfolded protein response, chaperones (Hsp70, Hsp90), and proteasomal machinery. Genes and proteins involved in apoptosis and senescence pathways are downregulated because of p53 amyloid accumulation, making the cell susceptible to oncogenic transformation. Additionally, because of the production of p53 amyloid, genes involved in cellular signaling that promote cell cycle and proliferation (CDKs, MAPK, ERK, CDCs, and Ras) are elevated concurrently. These pro-oncogenic genes give cells harboring p53 aggregates benefits in growth, migration, and survival. Furthermore, EMT, stemness, chemoresistance, and metastasis are caused by the overexpression of proteins in translational and metabolic pathways