Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy.
Akshatha Handattu ShankaranarayanaBhagyalalitha MeduriGurubasavaraj Veeranna PujarRaghu Chandrashekhar HariharapuraArun Kumar SethuManisha SinghDurgesh BidyePublished in: Future medicinal chemistry (2023)
Functional inactivation of wild-type p53 is a major trait of cancerous cells. In many cases, such inactivation occurs by either TP53 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.
Keyphrases
- wild type
- induced apoptosis
- heat shock protein
- drug discovery
- cancer therapy
- cell cycle arrest
- oxidative stress
- cell proliferation
- poor prognosis
- endoplasmic reticulum stress
- binding protein
- cell death
- transcription factor
- signaling pathway
- dna methylation
- dna binding
- gene expression
- heat shock
- genome wide
- squamous cell
- antiretroviral therapy
- hiv infected