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Other areas, however, containaggregates ofthin filaments and cytoplasmic densities (arrows), featuresthat are characteristic of smooth muscle cells. The physiological signicance of this auto-regulatory feedback loop was demonstrated by the clinical observation that ampli -cation of Hdm2 in human cancers often correlates with wild type p53 status,supporting the notion that high expression of Hdm2 is sufcient for relieving a cellfrom p53 regulation, in the absence of p53 mutation (reviewed in [27, 28, 2]).Further, a single nucleotide polymorphism (SNP) in the hdm2 gene that leads toincrease Hdm2 expression, results in reduced levels of p53-dependent apoptosis andcorrelates with accelerated tumour formation [29] (for review see [30, 31]).Consistently, reduced expression of Mdm2 protein in mice carrying a hypomorphicmdm2 allele, results in increased frequency of p53 dependent apoptosis and leads tomany defects in mice [32] (or reviewed in [30, 33])

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