p53 activates transcription of genes with a p53 response element, and it can repress genes lacking the element. Here we demonstrate that wild-type but not mutant p53 inhibits transcription in a HeLa nuclear extract from minimal promoters. Wild-type but not mutant p53 binds to human TATA-binding protein (TBP). p53 does not bind to yeast TBP, and it cannot inhibit transcription in a HeLa extract ...

UV light induces the expression of a wide variety of genes. At present, it is unclear how cells sense the extent of DNA damage and alter the expression of UV-induced genes appropriately. UV light induces DNA damage that blocks transcription, and the probability that a gene sustains transcription-blocking DNA damage is proportional to locus size and dose of UV light. Using colon carcinoma cells ...

In an effort to identify genes whose expression is regulated by activated phosphatidylinositol 3-kinase (PI3K) signaling, we performed microarray analysis and subsequent quantitative reverse transcription-PCR on an isogenic set of PTEN gene-targeted human cancer cells. Numerous p53 effectors were upregulated following PTEN deletion, including p21, GDF15, PIG3, NOXA, and PLK2. Stable depletion o...

How do regulatory switches achieve high sensitivity within the noisy cellular milieu? Loewer et al. (2010) now use single-cell microscopy to demonstrate that alternative posttranslational modifications allow the tumor suppressor p53 to differentiate between benign breaks in DNA during the cell cycle and deleterious damage caused by mutagens.

Nikolaev et al. (this issue of Cell) report the identification of a parkin-like protein, Parc, and its role in anchoring the tumor suppressor protein p53 in the cytoplasm reveals yet another level of control of p53 function. Regulation of the subcellular localization of p53 by Parc may serve as a novel target in treatment of certain types of tumors.

Reactivating the p53 pathway in tumors is an important strategy for anticancer therapy. In response to diverse cellular stresses, the tumor suppressor p53 mediates apoptosis in a transcription-independent and transcription-dependent manner. Although extensive studies have focused on the transcription-dependent apoptotic pathway of p53, the transcription-independent apoptotic pathway of p53 has ...

The tumor suppressor gene p53 is known to induce G1-S and G2-M cell cycle arrest and apoptosis by transactivating various wild-type (WT) p53 regulatory genes. Mutational inactivation of p53 is detected in more than half of human cancers, depriving the p53 protein of its tumor-suppressive functions. Recent studies have shown that mutant p53 provides tumor cells with gain-of-function properties, ...

Title: A combined analysis of the Deleted in Colon Cancer (DCC) and the p53 proteins expression in gastric cancer. Summary Background: Loss of acitivity of tumor suppressor genes is considered a fundamental step in a genetic model of

Encoded by the mutated variants of the TP53 tumor suppressor gene, mutant p53 proteins are getting an increased experimental support as active oncoproteins promoting tumor growth and metastasis. p53 missense mutant proteins are losing their wild-type tumor suppressor activity and acquire oncogenic potential, possessing diverse transforming abilities in cell and mouse models. Whether various mut...

p53 is a pleiotropic transcription factor driving a flexible transcriptional program that mediates disparate cellular responses to stress, including cell cycle arrest and apoptosis. The mechanisms by which p53 differentially regulates its diverse target genes remain poorly understood. In this issue of Genes & Development, Morachis and colleagues (pp. 135-147) demonstrate the critical role of co...