Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment
Cancer is an uncontrolled and abnormal growth of cells in the body. Gene that guards the cell cycle and function as tumor suppressor is p53 (also called as the guardian of the genome) which is encoded by the TP53 gene. Various events like DNA damage, heat shock, hypoxia and oncogene over expression,...
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doaj-ef05005918eb40bc8861cde6d83a66c32021-05-21T04:16:28ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-01-01109484492Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatmentAmit Gupta0Karan Shah1Manisha J. Oza2Tapan Behl3Animal Tissue Culture Laboratory, Department of Pharmacology, Indo Soviet Friendship College of Pharmacy, Moga, Punjab, IndiaDepartment of Pharmacology, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, IndiaSVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, IndiaDepartment of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India; Corresponding author at: Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.Cancer is an uncontrolled and abnormal growth of cells in the body. Gene that guards the cell cycle and function as tumor suppressor is p53 (also called as the guardian of the genome) which is encoded by the TP53 gene. Various events like DNA damage, heat shock, hypoxia and oncogene over expression, results in activation of p53.Thus, it plays a major role as a regulatory protein which regulates various diverse biological responses, responsible for genetic stability by preventing genome mutation. More than 50% mutations in human cancers along with the increase in expression of murine double minute 2 gene (mdm2), has been found as one of the reason for cancer progression. Murine double minute 2 (MDM2) is the negative regulator of p53 gene forming an autoregulatory feedback loop controlling each other cellular levels. Murine double minute 2 is unique E3 ubiquitin ligase protein which is responsible for ubiquitination and degradation of p53 gene. Many drugs/compounds have been developed for reactivation of p53 gene by inhibiting MDM2 interaction with p53, using MDM2 antagonism, inhibiting E3 ubiquitination of p53. Many compounds have entered clinical trials in haematological malignancies. This review will throw some light on reactivation of p53 gene by MDM2 and its homologues.http://www.sciencedirect.com/science/article/pii/S075333221835296XMutationsNegative regulatorE3 ubiquitin ligaseUbiquitinationAntagonism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amit Gupta Karan Shah Manisha J. Oza Tapan Behl |
spellingShingle |
Amit Gupta Karan Shah Manisha J. Oza Tapan Behl Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment Biomedicine & Pharmacotherapy Mutations Negative regulator E3 ubiquitin ligase Ubiquitination Antagonism |
author_facet |
Amit Gupta Karan Shah Manisha J. Oza Tapan Behl |
author_sort |
Amit Gupta |
title |
Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment |
title_short |
Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment |
title_full |
Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment |
title_fullStr |
Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment |
title_full_unstemmed |
Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment |
title_sort |
reactivation of p53 gene by mdm2 inhibitors: a novel therapy for cancer treatment |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-01-01 |
description |
Cancer is an uncontrolled and abnormal growth of cells in the body. Gene that guards the cell cycle and function as tumor suppressor is p53 (also called as the guardian of the genome) which is encoded by the TP53 gene. Various events like DNA damage, heat shock, hypoxia and oncogene over expression, results in activation of p53.Thus, it plays a major role as a regulatory protein which regulates various diverse biological responses, responsible for genetic stability by preventing genome mutation. More than 50% mutations in human cancers along with the increase in expression of murine double minute 2 gene (mdm2), has been found as one of the reason for cancer progression. Murine double minute 2 (MDM2) is the negative regulator of p53 gene forming an autoregulatory feedback loop controlling each other cellular levels. Murine double minute 2 is unique E3 ubiquitin ligase protein which is responsible for ubiquitination and degradation of p53 gene. Many drugs/compounds have been developed for reactivation of p53 gene by inhibiting MDM2 interaction with p53, using MDM2 antagonism, inhibiting E3 ubiquitination of p53. Many compounds have entered clinical trials in haematological malignancies. This review will throw some light on reactivation of p53 gene by MDM2 and its homologues. |
topic |
Mutations Negative regulator E3 ubiquitin ligase Ubiquitination Antagonism |
url |
http://www.sciencedirect.com/science/article/pii/S075333221835296X |
work_keys_str_mv |
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