Unravelling the p53 misfolding by chaperones in cancer

Cancer appears to be a significant global public health concern and most prevalent leading cause of death worldwide. Delays in the diagnosis and treatment may lead to an increase in the prevalence of advanced-stage disease and death. Therefore, creating innovative diagnostic instruments and treatments that demonstrate high effectiveness is imperative. The majority of malignancies have dysfunction in the p53 pathway. In addition, p53 becomes dysfunctional and tends to undergo misfolding and aggregation, resulting in the creation of amyloid aggregates. Efforts are underway to investigate methods for reinstating the regular functioning and manifestation of p53. In this study, we have investigated Heat shock proteins (HSPs), which are molecular chaperones that play a significant role in various cellular processes such as intercellular transportation, formation or disintegration of complex protein, stabilisation or degradation of aggregated or misfolded proteins and protein folding. HSP40, also known as JDPs, are distinguished by their highly conserved J-domains. These domains facilitate the ability to bind to HSP70 and as a co-chaperone enhance the activity of ATPase. Emerging evidence indicates that HSP70/JDPs can influence the levels and/or functions of both wild-type and mutant p53. Only a small number of HSP40/JDPs, including C7, C2, B9, B1, A3, and DNAJA1, have been seen to influence the functions of both WT-p53 and Mut-p53. However, out of the sixteen members, only these handful are implicated in the advancement of cancer. Therefore, studying other HSP40/JDPs that are involved in the advancement of cancer and the activities of p53 (both mutant and wild type), together with their related processes, would enhance our understanding of how cancer progresses, we might potentially speed up the development of innovative treatments for cancer. It is expected that pharmacological molecules and their analogues that specifically target p53 aggregation might be utilised with other anticancer drugs to address the issue of p53 aggregation.