نتایج جستجو برای: mdm2 protein

تعداد نتایج: 1237193  

2016
Arundhati Banerjee Sujay Ray

Structural basis for exploration into MDM2 and MDM2-DHFR interaction plays a vital role in analyzing the obstruction in folate metabolism, nonsynthesis of purines, and further epigenetic regulation in Homo sapiens. Therefore, it leads to suppression of normal cellular behavior and malignancy. This has been earlier documented via yeast two-hybrid assays. So, with a novel outlook, this study expl...

Journal: :Annals of Oncology 2022

Glioblastoma (GBM) is one of the deadliest cranial tumors occurring in adults. Various biomarkers have been tested for their significance diagnosis, prognosis, and treatment GBM. Some well-studied markers GBM are Isocitrate dehydrogenase1 (IDH1), Murine double minute2 (MDM2), Epidermal Growth Factor Receptor (EGFR) p53. The aim this study was to investigate protein expression these patients Pak...

Journal: :Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2006
Robert C Millikan Kimberley Heard Scott Winkel Edgar J Hill Kristin Heard Beri Massa Lydia Mayes Patricia Williams Rachel Holston Kathleen Conway Sharon Edmiston Allan René de Cotret

MDM2, a protein that binds and inactivates the tumor suppressor p53, is overexpressed in a variety of human cancers (1). Bond et al. (2) recently identified a single nucleotide polymorphism in the MDM2 gene, 309 T/G within the MDM2 promoter (database for single nucleotide polymorphism reference sequence number 2279744; http:// snp500cancer.nci.nih.gov). The G allele showed increased affinity fo...

Journal: :Sarcoma 1997
Raphael E. Pollock Aiquing Lang Adel K. El-Naggar Robert Radinsky Mien Chie Hung

Purpose. MDM2 is an oncogene whose protein product may promote tumorigenesis by blocking wild-type p53 tumor suppressor mediated G (0)/G(1) cell cycle arrest, thereby inhibiting repair of damaged DNA prior to cell division. While MDM2 DNA amplification is frequently observed in human sarcoma, the mechanisms linking this amplification to MDM2 oncoprotein over-production as well as its functional...

2014
Takashi Nagata Kie Shirakawa Naohiro Kobayashi Hirokazu Shiheido Noriko Tabata Yuko Sakuma-Yonemura Kenichi Horisawa Masato Katahira Nobuhide Doi Hiroshi Yanagawa Jody Michael Mason

The oncoprotein MDM2 binds to tumor suppressor protein p53 and inhibits its anticancer activity, which leads to promotion of tumor cell growth and tumor survival. Abrogation of the p53:MDM2 interaction reportedly results in reactivation of the p53 pathway and inhibition of tumor cell proliferation. We recently performed rigorous selection of MDM2-binding peptides by means of mRNA display and id...

2012
Dirk Bohmann

Two RING fingers and DRIL1 (TRIAD1) is a proapoptotic protein that promotes p53 activation in several cancer cell lines, including MCF7, U2OS and A549 cells. In this study, we demonstrated that TRIAD1 is a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). TRIAD1 was found to interact with and be ubiquitinated by MDM2. RNA interference against MDM...

2002
Lubing Gu Harry W. Findley Muxiang Zhou

MDM2 protein is thought to exhibit tumorigenic activity by binding to the p53 tumorsuppressor protein and inhibiting its function. Alternatively, MDM2 may have oncogenic roles other than those resulting from p53 interactions. Here we report that MDM2 can induce expression of the p65 subunit of NFB, which is an antiapoptotic factor expressed in certain neoplastic cells in response to chemotherap...

Journal: :Cancers 2016
M Lee Schmidt Diego F Calvisi Geoffrey J Clark

Mouse Double Minute 2 Homolog (MDM2) is a key negative regulator of the master tumor suppressor p53. MDM2 regulates p53 on multiple levels, including acting as an ubiquitin ligase for the protein, thereby promoting its degradation by the proteasome. MDM2 is oncogenic and is frequently found to be over-expressed in human tumors, suggesting its dysregulation plays an important role in human cance...

2016
Maciej Pawel Ciemny Aleksander Debinski Marta Paczkowska Andrzej Kolinski Mateusz Kurcinski Sebastian Kmiecik

Protein-peptide interactions are often associated with large-scale conformational changes that are difficult to study either by classical molecular modeling or by experiment. Recently, we have developed the CABS-dock method for flexible protein-peptide docking that enables large-scale rearrangements of the protein chain. In this study, we use CABS-dock to investigate the binding of the p53-MDM2...

Journal: :Journal of medicinal chemistry 2012
Yosup Rew Daqing Sun Felix Gonzalez-Lopez De Turiso Michael D Bartberger Hilary P Beck Jude Canon Ada Chen David Chow Jeffrey Deignan Brian M Fox Darin Gustin Xin Huang Min Jiang Xianyun Jiao Lixia Jin Frank Kayser David J Kopecky Yihong Li Mei-Chu Lo Alexander M Long Klaus Michelsen Jonathan D Oliner Tao Osgood Mark Ragains Anne Y Saiki Steve Schneider Maria Toteva Peter Yakowec Xuelei Yan Qiuping Ye Dongyin Yu Xiaoning Zhao Jing Zhou Julio C Medina Steven H Olson

Structure-based rational design led to the discovery of novel inhibitors of the MDM2-p53 protein-protein interaction. The affinity of these compounds for MDM2 was improved through conformational control of both the piperidinone ring and the appended N-alkyl substituent. Optimization afforded 29 (AM-8553), a potent and selective MDM2 inhibitor with excellent pharmacokinetic properties and in viv...

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