Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, RJ 21941-901 Rio de Janeiro, Brazil.
Department of Biochemistry and Immunology, Federal University of Minas Gerais, MG 31270-901 Belo Horizonte, Brazil.
Biomolecules. 2020 Apr 4;10(4):548. doi: 10.3390/biom10040548.
Despite being referred to as the guardian of the genome, when impacted by mutations, p53 can lose its protective functions and become a renegade. The malignant transformation of p53 occurs on multiple levels, such as altered DNA binding properties, acquisition of novel cellular partners, or associating into different oligomeric states. The consequences of these transformations can be catastrophic. Ongoing studies have implicated different oligomeric p53 species as having a central role in cancer biology; however, the correlation between p53 oligomerization status and oncogenic activities in cancer progression remains an open conundrum. In this review, we summarize the roles of different p53 oligomeric states in cancer and discuss potential research directions for overcoming aberrant p53 function associated with them. We address how misfolding and prion-like amyloid aggregation of p53 seem to play a crucial role in cancer development. The misfolded and aggregated states of mutant p53 are prospective targets for the development of novel therapeutic strategies against tumoral diseases.
尽管被称为基因组的守护者，但当受到突变影响时，p53 可能会失去其保护功能，变成一个叛逆者。p53 的恶性转化发生在多个层面上，例如改变 DNA 结合特性、获得新的细胞伙伴，或形成不同的寡聚状态。这些转化的后果可能是灾难性的。正在进行的研究表明，不同的寡聚 p53 物种在癌症生物学中具有核心作用；然而，p53 寡聚状态与癌症进展中的致癌活性之间的相关性仍然是一个悬而未决的难题。在这篇综述中，我们总结了不同 p53 寡聚状态在癌症中的作用，并讨论了克服与它们相关的异常 p53 功能的潜在研究方向。我们探讨了 p53 的错误折叠和类朊病毒样淀粉样聚集如何在癌症发展中发挥关键作用。突变型 p53 的错误折叠和聚集状态是开发针对肿瘤疾病的新型治疗策略的潜在目标。
