Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy

Akshatha Handattu Shankaranarayana; Bhagyalalitha Meduri; Gurubasavaraj Veeranna Pujar; Raghu Chandrashekar Hariharapura; Arun Kumar Sethu; Manisha Singh; Durgesh Bidye

doi:10.4155/fmc-2023-0061

Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy

Akshatha Handattu Shankaranarayana, Bhagyalalitha Meduri, Gurubasavaraj Veeranna Pujar, Raghu Chandrashekar Hariharapura, Arun Kumar Sethu, Manisha Singh, Durgesh Bidye

Research output: Contribution to journal › Review article › peer-review

3 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2087-2112
Number of pages	26
Journal	Future Medicinal Chemistry
Volume	15
Issue number	22
DOIs	https://doi.org/10.4155/fmc-2023-0061
Publication status	Published - 01-11-2023

All Science Journal Classification (ASJC) codes

Molecular Medicine
Pharmacology
Drug Discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4155/fmc-2023-0061

Cite this

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title = "Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy",

abstract = "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.",

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T2 - an emerging target in cancer therapy

AU - Shankaranarayana, Akshatha Handattu

AU - Meduri, Bhagyalalitha

AU - Pujar, Gurubasavaraj Veeranna

AU - Hariharapura, Raghu Chandrashekar

AU - Sethu, Arun Kumar

AU - Singh, Manisha

AU - Bidye, Durgesh

PY - 2023/11/1

Y1 - 2023/11/1

N2 - 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.

AB - 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.

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Restoration of p53 functions by suppression of mortalin-p53 sequestration: an emerging target in cancer therapy

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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