MDM2 inhibition: an important step forward in cancer therapy
Jul 10, 2020 · MDM2 then inhibits the p53-mediated transcription of MDM2 and other downstream target genes by binding to p53, blocking its transactivation domain. Through E3 ubiquitin ligase activity,...
The MDM2-p53 pathway revisited - PMC - National Center for ...
Jun 6, 2013 · The p53 tumor suppressor is a key transcription factor regulating cellular pathways such as DNA repair, cell cycle, apoptosis, angiogenesis, and senescence. It acts as an important defense mechanism against cancer onset and progression, and is negatively regulated by interaction with the oncoprotein MDM2.
A structure-based virtual screening identifies a novel MDM2 …
Oct 9, 2024 · The overexpression or amplification of MDM2 is commonly observed in various human cancers bearing wild-type p53 alleles, leading to the rapid degradation of the p53 protein and the attenuation of ...
Therapeutic opportunities in cancer therapy: targeting the p53-MDM2 …
Dec 15, 2021 · The p53-MDM2-MDMX pathway provides multiple molecular targets for small molecule screening as potential therapies for wild-type p53. As a result of its effect on molecular carcinogenesis, a personalized therapeutic approach based on the wild-type and mutant p53 protein is desirable.
A first-in-human phase I study of a novel MDM2/p53 inhibitor ...
Introduction. The genetic alteration of TP53 occurs in ∼50% of human tumors.1, 2, 3 Furthermore, diverse molecular mechanisms inhibit the antitumor function of p53. Among these, mouse double minute 2 homolog (MDM2) is a potent negative regulator of p53.4, 5, 6 MDM2 and p53 proteins influence each other through an autoregulating feedback loop. 7 …
Mdm2-mediated ubiquitylation: p53 and beyond - Nature
Jun 5, 2009 · A key Mdm2 function is to promote ubiquitylation and proteasomal-dependent degradation of the tumor suppressor protein p53. Recent reports provide novel important insights into Mdm2-mediated...
MDM2: current research status and prospects of tumor treatment
May 13, 2024 · MDM2 influences tumor development and progression in breast cancer through multiple pathways. Firstly, P21 is a downstream cell cycle protein kinase inhibitor of P53, and in breast cancer, it can block cell cycle progression, exerting an anti-cancer effect.
The role of the MDM2/p53 axis in antitumor immune responses
Jun 27, 2024 · Mouse double minute 2 homolog (MDM2) is a negative regulator of the tumor suppressor p53 and is often highly expressed in acute myeloid leukemia (AML) and other solid tumors. Inactivating mutations in TP53, the gene encoding p53, confers an unfavorable prognosis in AML and increases the risk for relapse after allogeneic hematopoietic cell ...
The MDM2-p53 pathway revisited - PubMed
The p53 tumor suppressor is a key transcription factor regulating cellular pathways such as DNA repair, cell cycle, apoptosis, angiogenesis, and senescence. It acts as an important defense mechanism against cancer onset and progression, and is negatively regulated by interaction with the oncoprotein ….
Structural Details on mdm2-p53 Interaction - Journal of …
Molecular Modeling—A structural model for the complex of mdm2 with p53 turn II motif was generated using the molecular modeling package Insight II on a Silicon Graphics O 2 work station. On the basis of transferred NOE data, the turn II peptide of p53 was modeled into an ideal α-helix using the builder and biopolymer modules of Insight II.
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