We investigated p53-dependent gene expression in nitric oxide (NO)-induced apoptosis of two tumor cell types. Seventy-seven putative p53-regulated genes were screened for NO-mediated expression changes. Twenty-four genes were up-regulated and three genes were down-regulated significantly by NO in human neuroblastoma cells. Genes known to be involved in apoptosis, which were up-regulated by > or...

Elevated cAMP levels in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells attenuate the doxorubicin-induced p53 accumulation and protect cells against apoptosis. cAMP responsive element binding protein (CREB) is a cAMP-stimulated transcription factor that regulates genes whose deregulated expression cooperatein oncogenesis. In the present study, we investigated the role of CREB on i...

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...

We have developed a novel computational alanine scanning approach that involves analysis of ensemble unfolding kinetics at high temperature to identify residues that are critical for the stability of a given protein. This approach has been applied to dimerization of the oligomerization domain (residues 326-355) of tumor suppressor p53. As validated by experimental results, our approach has reas...

'Simplify your life.' In research-contrasting such a popular concept-we are challenged by an ever-expanding plethora of observations and accumulation of knowledge. This leads to the development of increasingly complex models trying to explain all aspects of our world that are subject to scientific endeavor. Recently, a well-known object of study from the life sciences, the tumor suppressor p53,...

Wild-type p53 and TGF-β are key tumour suppressors which regulate an array of cellular responses. TGF-β signals in part via the Smad signal transduction pathway. Wild-type p53 and Smads physically interact and coordinately induce transcription of a number of key tumour suppressive genes. Conversely mutant p53 generally subverts tumour suppressive TGF-β responses, diminishing transcriptional act...

Multiple genetic alterations, including inactivation of the p53 and RB genes and loss of heterozygosity on chromosome 3p, occur commonly in small cell lung carcinoma (SCLC). To assess the biological significance of p53 inactivation in the development of SCLC, tetracycline (Tc)-inducible p53 expression plasmids were introduced into a SCLC cell line, N417, in which the p53 gene as well as the RB ...

The predominant function of the tumor suppressor p53 is transcriptional regulation. It is generally accepted that p53-dependent transcriptional activation occurs by binding to a specific recognition site in promoters of target genes. Additionally, several models for p53-dependent transcriptional repression have been postulated. Here, we evaluate these models based on a computational meta-analys...

The wild-type p53 protein is a DNA-binding transcription factor that activates genes such as p21, MDM2, GADD45, and Bax that are required for the regulation of cell cycle progression or apoptosis in response to DNA damage. Mutant forms of p53, which are transforming oncogenes and are expressed at high levels in tumor cells, generally have a reduced binding affinity for the consensus DNA sequenc...

Ionizing radiation is a potent activator of the tumor suppressor gene p53, which itself regulates the transcription of genes involved in canonical pathways such as the cell cycle, DNA repair and apoptosis as well as other biological processes like metabolism, autophagy, differentiation and development. In this study, we performed a meta-analysis on gene expression data from different in vivo an...