Functional reactivation of p53 pathway, although arduous, can potentially provide a broad-based strategy for cancer therapy owing to frequent p53 inactivation in human cancer. Using a phosphoprotein-screening array, we found that Benzyl Isothiocynate, (BITC) increases p53 phosphorylation in breast cancer cells and reveal an important role of ERK and PRAS40/MDM2 in BITC-mediated p53 activation. ...

The binding of MDM2 targets p53, but not p73, for degradation, whereas it suppresses the transactivation function of both proteins. MDM2 also mediates p53 nuclear export, but its role in the regulation of p73 distribution is unknown at the present time. We show here that, in sharp contrast to p53, MDM2 induces p73 to form nuclear aggregates that colocalize with MDM2 but are distinct from the pr...

p73 has been identified as a structural and functional homolog of the tumor suppressor p53. The transcriptional coactivator Yes-associated protein (YAP) has been demonstrated to interact with and to enhance p73-dependent apoptosis in response to DNA damage. Here, we show the existence of a proapoptotic autoregulatory feedback loop between p73, YAP, and the promyelocytic leukemia (PML) tumor sup...

Multiple adenovirus (Ad) early proteins have been shown to inhibit transcription activation by p53 and thereby to alter its normal biological functioning. Since these Ad proteins affect the activity of p53 via different mechanisms, we examined whether this inhibition is target gene specific. In addition, we analyzed whether the same Ad early proteins have a comparable effect on transcription ac...

1alpha,25-Dihydroxyvitamin D3 (1,25D3) exhibits antitumor activity in a variety of cancers including squamous cell carcinoma (SCC). Intrinsic resistance of SCC cells to cisplatin was observed and led to the investigation into whether 1,25D3 sensitizes SCC cells to cisplatin. Pretreatment with 1,25D3 followed by cisplatin enhanced growth inhibition in SCC cells compared with 1,25D3 alone as asse...

The p53 gene encodes one of the most important tumor suppressors in human cells and undergoes frequent mutational inactivation in cancers. MDM2, a transcriptional target of p53, binds p53 and can both inhibit p53-mediated transcription [1] [2] and target p53 for proteasome-mediated proteolysis [3] [4]. A close relative of p53, p73, has recently been identified [5] [6]. Here, we report that, lik...

Although microRNAs (miRNAs) are important regulators of gene expression, the transcriptional regulation of miRNAs themselves is not well understood. We employed an integrative computational pipeline to dissect the transcription factors (TFs) responsible for altered miRNA expression in ovarian carcinoma. Using experimental data and computational predictions to define miRNA promoters across the h...

Introduction p53 continues to be one of the most intensively studied genes in cancer biology. p53 was initially identified .20 years ago as a binding partner for the SV40 T oncoprotein. Further studies revealed that p53 is a tumor suppressor gene that is mutated or inactivated in .50% of human cancers. Furthermore, germ-line p53 mutations cause hereditary cancer in both mice and humans. Molecul...

Recently, several proteins have been identified that are related in their sequence to the p53 tumor-suppressor protein. One of these proteins, which is termed p73, exhibits sequence homology to the p53 transcriptional activation, DNA binding, and oligomerization domains. The adenovirus E1B 55-kDa protein, the adenovirus E4orf6 protein, and SV40 T antigen each can bind to p53 and inhibit p53 fun...

OBJECTIVES p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS). METHODS In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS. RESULTS We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methyl...