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The DNA binding activity of p53 is required for its tumor suppressor function; we show here that this activity is cryptic but can be activated by cellular factors acting on a C-terminal regulatory domain of p53. A gel mobility shift assay demonstrated that recombinant wild-type human p53 binds DNA sequence specifically only weakly, but a monoclonal antibody(More)
The p53 tumour suppressor is induced by various stress stimuli and coordinates an adaptive gene expression programme leading to growth arrest or cell death. Some stimuli, such as DNA damage, lead to rapid and substantial multisite phosphorylation of p53, nucleated initially through phosphorylation of serine 15. Other stimuli, such as hyper-proliferation, do(More)
Polo-like kinase-1 (PLK1) is a crucial driver of cell cycle progression and its down-regulation plays an important checkpoint role in response to DNA damage. Mechanistically, this is mediated by p53 which represses PLK1 expression through chromatin remodelling. Consistent with this model, cultured cells lacking p53 fail to repress PLK1 expression. This(More)
The RNA helicase p68 (DDX5) is an established co-activator of the p53 tumour suppressor that itself has a pivotal role in orchestrating the cellular response to DNA damage. Although several factors influence the biological outcome of p53 activation, the mechanisms governing the choice between cell-cycle arrest and apoptosis remain to be elucidated. In the(More)
Here we define an important role for heat shock factor 1 (HSF1) in the cellular response to genotoxic agents. We demonstrate for the first time that HSF1 can complex with nuclear p53 and that both proteins are co-operatively recruited to p53-responsive genes such as p21. Analysis of natural and synthetic cis elements demonstrates that HSF1 can enhance(More)
Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that has been implicated in the progression of breast, pancreatic and colorectal cancer (CRC). To determine mechanisms underlying growth promotion by LRH-1 in CRC, we undertook global expression profiling following siRNA-mediated LRH-1 knockdown in HCT116 cells, which require LRH-1 for growth(More)
Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several(More)
Solar ultraviolet (UV) radiation promotes skin tumorigenesis by inducing DNA damage. UV radiation activates cellular stress responses involving induction of transcription factor p53 and adaptive changes in transcriptional patterns of the cells. p53 is the most often mutated gene in human cancers, indicating its essential role in tumor suppression. Upon UV(More)
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