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A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans
The tumor suppressor p53 gene is mutated in minimally half of all cancers. It is therefore reasonable to assume that naturally occurring polymorphic genetic variants in the p53 stress response… Expand
Gain of Function of a p53 Hot Spot Mutation in a Mouse Model of Li-Fraumeni Syndrome
Individuals with Li-Fraumeni syndrome carry inherited mutations in the p53 tumor suppressor gene and are predisposed to tumor development. To examine the mechanistic nature of these p53 missense… Expand
Pirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 Degradation
The p53 tumor suppressor exerts anti-proliferative effects in response to various types of stress including DNA damage and abnormal proliferative signals. Tight regulation of p53 is essential for… Expand
Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
THE gene p53 encodes a transcriptional activator1,2 of genes involved in growth arrest3,4, DNA repair5 and apoptosis6–8. Loss of p53 function contributes to tumour development in vivo 9–11. The… Expand
Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2
In response to environmental stress, the p53 phosphoprotein is stabilized and activated to inhibit cell growth. p53 stability and activity are negatively regulated by the murine double minute (Mdm2)… Expand
Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53
The p53 protein can inhibit cell cycling or induce apoptosis, and is thus a critical regulator of tumorigenesis. This protein is negatively regulated by a physical interaction with MDM2, an E3… Expand
Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor.
The constitutive androstane receptor (CAR, NR1I3) is a central regulator of xenobiotic metabolism. CAR activation induces hepatic expression of detoxification enzymes and transporters and increases… Expand
The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss.
The p53 tumor suppressor is often disrupted in human cancers by the acquisition of missense mutations. We generated mice with a missense mutation at codon 172 that mimics the p53R175H hot spot… Expand
Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice
The p53 protein integrates multiple upstream signals and functions as a tumor suppressor by activating distinct downstream genes. At the cellular level, p53 induces apoptosis, cell cycle arrest and… Expand
p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer.
Studies on the role of TP53 mutation in breast cancer response to chemotherapy are conflicting. Here, we show that, contrary to dogma, MMTV-Wnt1 mammary tumors with mutant p53 exhibited a superior… Expand