Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Sri Shivarathreeshwara Nagara, Mysuru, 570015, India.
Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, India.
Future Med Chem. 2023 Nov;15(22):2087-2112. doi: 10.4155/fmc-2023-0061. Epub 2023 Oct 25.
Functional inactivation of wild-type p53 is a major trait of cancerous cells. In many cases, such inactivation occurs by either gene mutations or due to overexpression of p53 binding partners. This review focuses on an overexpressed p53 binding partner called mortalin, a mitochondrial heat shock protein that sequesters both wild-type and mutant p53 in malignant cells due to changes in subcellular localization. Clinical evidence suggests a drastic depletion of the overall survival time of cancer patients with high mortalin expression. Therefore, mortalin-p53 sequestration inhibitors could be game changers in improving overall survival rates. This review explores the consequences of mortalin overexpression and challenges, status and strategies for accelerating drug discovery to suppress mortalin-p53 sequestration.
野生型 p53 的功能失活是癌细胞的主要特征。在许多情况下，这种失活要么是由于基因突变，要么是由于 p53 结合伴侣的过度表达。本综述重点介绍了一种过度表达的 p53 结合伴侣，称为 mortalin，它是一种线粒体热休克蛋白，由于亚细胞定位的变化，将野生型和突变型 p53 隔离在恶性细胞中。临床证据表明，高 mortalin 表达的癌症患者的总生存时间明显减少。因此，mortalin-p53 隔离抑制剂可能会改变提高总生存率的局面。本综述探讨了 mortalin 过表达的后果和挑战，以及加速药物发现以抑制 mortalin-p53 隔离的现状和策略。
