Maf transcriptionally activates the mouse p53 promoter and causes a p53-dependent cell death.

An increase in the level of the tumor suppressor protein p53 can induce cell cycle arrest or cell death. Although mechanisms for regulating the life span of p53 have been described, there is growing evidence that transcriptional regulation of the p53 gene contributes significantly to controlling p53 protein levels and therefore the fate of a cell. However, the signal transduction pathways that lead to transcriptional activation of the p53 gene are poorly understood.

Inhibition of SV40 large T antigen induced apoptosis by small T antigen.

It is well established that the expression of simian virus 40 (SV40) early gene products causes oncogenic transformation of rodent cells. An important aspect of this process is the inactivation of the p53 and retinoblastoma (pRb) tumour suppressor proteins through interaction with the SV40 large tumour antigen (LT). In addition, the SV40 small tumour antigen (ST) may enhance LT induced transformation.

MDM2 is a target of simian virus 40 in cellular transformation and during lytic infection.

Phosphopeptide analyses of the simian virus 40 (SV40) large tumor antigen (LT) in SV40-transformed rat cells, as well as in SV40 lytically infected monkey cells, showed that gel-purified LT that was not complexed to p53 (free LT) and p53-complexed LT differed substantially in their phosphorylation patterns. Most significantly, p53-complexed LT contained phosphopeptides not found in free LT. We show that these additional phosphopeptides were derived from MDM2, a cellular antagonist of p53, which coprecipitated with the p53-LT complexes, probably in a trimeric LT-p53-MDM2 complex.

Cell-specific transcriptional activation of the mdm2-gene by ectopically expressed wild-type form of a temperature-sensitive mutant p53.

The temperature-sensitive mutant p53 tsp53val135 (tsp53) displays a mutant phenotype at 38 degrees C, but assumes properties of a wild-type (wt) p53 at 32 degrees C. We analysed the cellular responses of two cell lines which ectopically overexpress tsp53, and dramatically differ in their responses to tsp53 expressed at 32 degrees C. Clone 6 (cl6) cells [precrisis rat embryo fibroblasts transformed by tsp53val135 and an activated ras oncogene at 38 degrees C (Michalovitz et al.

Wild-type p53 in cellular-transformation - a reassessment.

We found that a mouse p53 cDNA clone (pP53-5; Jenkins et al, Nature 312: 651-654, 1984), which previously was characterized as encoding mutant p53 protein, in fact represents wild-type mouse p53 cDNA, as we were able to demonstrate that the mutations described represented sequencing artefacts (compressions). Such sequencing artefacts were also observed with a p53 cDNA isolated from mouse T3T3 cells, encoding a mutant p53 with an Arg-Cys exchange at position 270, and could be resolved by sequencing of the opposite DNA strands. As pP53-5 had been successfully used in cellular immortalization and transformation assays (Jenkins et al, Nature 312: 651-654, 1984; Nature 317: 816-818, 1985), our results suggest that wild-type p53 under certain circumstances can induce transformation.