Mutant p53: from guardian to fallen angel?

Deppert, Wolfgang

doi:10.1038/sj.onc.1210276

Cited by 12 publications

(7 citation statements)

References 5 publications

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“…Hence, our observations provide an explanation for the important question why p53 mutations rather than p53 deletions arise in tumors (Deppert, 2007;Soussi and Wiman, 2007). Consistent with this, it was found that chemotherapeutics, hypoxia and oncogene activation induce checkpoint activation, replicational arrest and selection for aberrant p53 (Hanahan and Weinberg, 2000;Janssens and Tschopp, 2006;Finkel et al, 2007;Marusyk and DeGregori, 2007;Kra¨mer, 2009;Viale et al, 2009).…”

Section: Control Of Activated Nf-jb By P53supporting

confidence: 67%

“…Inactivation of the p53 pathway is observed in most human cancers, with mutations in p53 occurring in at least 50% of all tumors (Soussi and Wiman, 2007). Interestingly, in addition to the lack of tumor suppressive functions, p53 mutants gain oncogenic activities contributing to carcinogenesis and drug resistance (Moll et al, 2005;Deppert, 2007;Vousden and Lane, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Cross talk between stimulated NF-κB and the tumor suppressor p53

et al. 2010

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Nuclear factor-jB (NF-jB) and p53 critically determine cancer development and progression. Defining the cross talk between these transcription factors can expand our knowledge on molecular mechanisms of tumorigenesis. Here, we show that induction of replicational stress activates NF-jB p65 and triggers its interaction with p53 in the nucleus. Experiments with knockout cells show that p65 and p53 are both required for enhanced NF-jB activity during S-phase checkpoint activation involving ataxiatelangiectasia mutated and checkpoint kinase-1. Accordingly, the pro-inflammatory cytokine tumor necrosis factora (TNF-a) also triggers formation of a transcriptionally active complex containing nuclear p65 and p53 on jB response elements. Gene expression analyses revealed that, independent of NF-jB activation in the cytosol, TNFinduced NF-jB-directed gene expression relies on p53. Hence, p53 is unexpectedly necessary for NF-jB-mediated gene expression induced by atypical and classical stimuli. Remarkably, data from gain-and loss-of function approaches argue that anti-apoptotic NF-jB p65 activity is constitutively evoked by a p53 hot-spot mutant frequently found in tumors. Our observations suggest explanations for the outstanding question why p53 mutations rather than p53 deletions arise in tumors of various origins.

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Section: Control Of Activated Nf-jb By P53supporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Cross talk between stimulated NF-κB and the tumor suppressor p53

et al. 2010

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“…Because the expression of mutant p53 in tumor cells has been associated with increased cell proliferation and survival (38,39), we sought to analyze the effect of PAs on cell cycle and apoptosis of two cancer cell lines (Sk-Br-3 and MDA-MB-468) bearing endogenous mutant p53 (respectively, p53R175H and p53R273H). To selectively analyze cells expressing the PAs, propidium-iodide staining was measured only in the EGFP-positive cell population.…”

Section: Pas Interfere With Mutant P53 Transactivating Functionsmentioning

confidence: 99%

Peptide Aptamers Targeting Mutant p53 Induce Apoptosis in Tumor Cells

et al. 2008

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“…Stable 3T3mutp53 C2 and C6 clones were maintained in DMEM supplemented with 5% FCS and 200 mg/ml G418 (Gibco). Cells were grown to subconfluent monolayers in 100 mm 2 dishes and infected with SV40 virus (strain 776) at a multiplicity of infection (MOI) of one, as previously described (Tiemann and Deppert, 1994). Virus incubation (2 h) at 371C continued altogether in complete medium for 34 h postinfection.…”

Section: Cells and Abortive Infectionmentioning

confidence: 99%