Mdm2 is a critical negative regulator of the p53 tumor suppressor and is frequently overexpressed in human cancers. However, reports, including our own studies, suggest that Mdm2 has both p53-dependent and p53-independent functions that contribute to genomic instability and transformation when deregulated. We recently elucidated a p53-independent role for Mdm2 in the regulation of the DNA doubl...

Induction of murine double minute 2 (MDM2) expression is thought to be a determinant of resistance to p53 gene therapy for cancer. Previous studies have revealed that ribosomal protein L23 (RPL23) inhibits MDM2-mediated p53 degradation through direct binding to MDM2. In addition, ectopically expressed RPL23 was reported to interact with MDM2 in both the nucleus and cytoplasm, by which RPL23 ind...

OBJECTIVE Human murine double minute 2 protein (MDM2) is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. METHODS A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase...

Since the initial discovery of mutations in the p53 (also known as TP53) gene in colorectal carcinoma, notable progress has been made in elucidating the role of p53 in the regulation of gene expression, cycle progression, and apoptosis (7). It is now recognized that p53 is induced in response to some types of DNA damage and that it is a key component of the physiologic checkpoint pathway that g...

Mouse double minute 2 (Mdm2) and MdmX dimerize in response to low levels of genotoxic stress to function in a ubiquitinating complex, which signals for destabilization of p53. Under growth conditions, Mdm2 functions as a neddylating ligase, but the importance and extent of MdmX involvement in this process are largely unknown. Here we show that when Mdm2 functions as a neddylating enzyme, MdmX i...

Cellular senescence is emerging as an important in vivo anticancer response elicited by multiple stresses, including currently used chemotherapeutic drugs. Nutlin-3a is a recently discovered small-molecule antagonist of the p53-destabilizing protein murine double minute-2 (MDM2) that induces cell cycle arrest and apoptosis in cancer cells with functional p53. Here, we report that nutlin-3a indu...

PURPOSE p53 is frequently expressed but rarely mutated in Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL). p53 protein levels are regulated by murine double minute 2 (MDM2) through a well-established autoregulatory feedback loop. In this study, we investigated the effects of nutlin-3A, a recently developed small molecule that antagonizes MDM2 and disrupts the p53-MDM2 interact...

Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimet...

Inhibition of HIF-1a activity provides an important strategy for the treatment of cancer. Recently, 3-(5 0-hydroxymethyl-2 0–furyl)-1benzyl indazole (YC-1) has been identified as an anti-HIF-1a drug in cancer therapy with unclear molecular mechanism. In the present study, we aimed to investigate the effect and mechanism of YC-1 on HIF-1a in a hepatocellular carcinoma cell line under hypoxic con...