High impact information on p53

• We describe a Drosophila p53 homolog and demonstrate that it can activate transcription from a promoter containing binding sites for human p53 [1].
• Dominant-negative forms of Drosophila p53 inhibit both transactivation in cultured cells and radiation-induced apoptosis in developing tissues [1].
• Unlike mammalian p53, Dmp53 appears unable to induce a G1 cell cycle block when overexpressed, and inhibition of Dmp53 activity does not affect X ray-induced cell cycle arrest [2].
• These results indicate that reaper is a direct transcriptional target of Drosophila p53 following DNA damage [1].
• The tumor suppressor gene p53 regulates multiple cellular responses to DNA damage, but the transcriptional targets that specify these responses are incompletely understood [1].

Associations of p53 with chemical compounds

• DN-Dmp53-dependent lifespan extension is accompanied by reduction of Drosophila insulin-like peptide 2 (dILP2) mRNA levels and reduced insulin signaling (IIS) in the fat body, which suggests that Dmp53 may affect lifespan by modulating insulin signaling in the fly [3].

Biological context of p53

• All undergo radiation-induced apoptosis. p53 mutants regulate the cell cycle but fail to undergo apoptosis [4].
• RESULTS: We find that dp53, the sole p53 ortholog in Drosophila, is required for each component of the response to cellular damage, including two separate cell-cycle arrests, changes in patterning gene expression, cell proliferation, and growth [5].
• CONCLUSIONS: DNA repair is essential for surviving radiation as expected; surprisingly, cell cycle regulation and p53-dependent cell death are not [4].
• BACKGROUND: The p53 transcription factor directs a transcriptional program that determines whether a cell lives or dies after DNA damage [5].
• Although the Drosophila p53 protein was previously shown to interact with the SAGA-like complex in vitro, we find that p53 induction of reaper gene expression occurs normally in dAda2b mutants [6].

Regulatory relationships of p53

• Although both the ecdysone hormone receptor complex and p53 directly regulate rpr transcription, rpr was found to play a limited role in inducing apoptosis in response to either of these signals [7].

Other interactions of p53

• We demonstrate that these processes are regulated by dp53 in a manner that is independent of DNA-damage sensing but that requires the initiator caspase Dronc [5].
• Moreover, dAda2b mutant animals show excessive p53-dependent apoptosis in response to gamma radiation [6].
• Three endogenous genes, Sir2, Sirt2, and p53 have been successfully deleted using this method [8].
• We also observed interactions with p53, which suggest that Wee1 and Myt1 activity can block apoptosis [9].
• Recently a Drosophila p53 protein has been identified that mediates apoptosis via a novel pathway involving the activation of the Reaper gene and subsequent inhibition of the inhibitors of apoptosis (IAPs) [10].

References