The orchestrated crosstalk between the retinoblastoma (RB) and p53 pathways contributes to preserving proper homeostasis within the cell. The deregulation of one or both pathways is a common factor in the development of most types of human cancer. The proto-oncoproteins MDMX and MDM2 are the main regulators of the well- known tumor suppressor p53 protein. Under normal conditions, MDM2 and MDMX ...

Mdm2 was first described 12 years ago. Interest in this oncogene has risen since its identification as a protein that binds and efficiently inactivates the p53 tumor suppressor protein. This interest was further boosted by the discovery that the mdm2 gene is actually a target for direct transcriptional activation by p53, thus defining an autoregulatory feedback loop for the intracellular modula...

Murine double minute homolog 2 (MDM2) is an oncoprotein that induces p53 degradation via ubiquitin‑ligase activity. MDM4 cooperates with MDM2‑mediated degradation, directly inhibiting transcription by binding to its transactivation domain. Our previous study reported the simultaneous inhibition of MDM2 and using nutlin‑3 (an inhibitor MDM2‑p53 interaction) chimeric small interfering RNA DNA‑sub...

Degradation of the p53 tumor suppressor protein has been shown to be regulated by Mdm2. In this study, we identify regions of Mdm2 that are not required for p53 binding but are essential for degradation. Mdm2 mutants lacking these regions function in a dominant negative fashion, stabilizing endogenous p53 in cells by interfering with the degradative function of the endogenous Mdm2. p53 protein ...

Murine double minute-2 protein (Mdm2) is a multifaceted phosphorylated protein that plays a role in regulating numerous proteins including the tumor suppressor protein p53. Mdm2 binds to and is involved in conjugating either ubiquitin or Nedd8 (Neural precursor cell expressed, developmentally down-regulated 8) to p53. Although regulation of the E3 ubiquitin activity of Mdm2 has been investigate...

BACKGROUND MDM2 is a negative regulator of p53 and is upregulated in numerous human cancers. While different MDM2 splice variants have been observed in both normal tissues and malignant cells, their functions are poorly understood. METHODS We evaluated the effect of MDM2 splice variants by overexpression in MCF-7 cells and analyses of expression of downstream genes (qPCR and Western blot), su...

The tumor suppressor p53 is commonly inhibited under conditions in which the phosphatidylinositide 3'-OH kinase/protein kinase B (PKB)Akt pathway is activated. Intracellular levels of p53 are controlled by the E3 ubiquitin ligase Mdm2. Here we show that PKB inhibits Mdm2 self-ubiquitination via phosphorylation of Mdm2 on Ser(166) and Ser(188). Stimulation of human embryonic kidney 293 cells wit...

Our previous studies have illustrated that CacyBP/SIP (Calcyclin-binding protein or Siah-1-interacting protein) promoted the proliferation of glioma cells. However, possible mechanism still needs to be clarified. In current study, we aimed uncover potential in regulating cell proliferation. We found decreased level p53, but not mRNA p53 mutant U251 line, whereas, wild-type U87 neither its nor r...

Nucleolar disassembly occurs during mitosis and nucleolar stress, releasing several MDM2-interactive proteins residing in the nucleolus that share the common activity of p53 stabilization. Here, we demonstrate that mobilization of nucleostemin, a nucleolar protein enriched in cancer and stem cells, has the opposite role of stabilizing MDM2 and suppressing p53 functions. Our results show that nu...

The tumor suppressor protein, p53, is either mutated or absent in >50% of cancers and is negatively regulated by the mouse double minute (MDM2) protein. Understanding and inhibition of the MDM2-p53 interaction are, therefore, critical for developing novel chemotherapeutics, which are currently limited because of a lack of appropriate study tools. We present a nanosensing approach to investigate...