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Tumor Suppressor p53's Contradictory Regulatory System

A new study appearing in the online open-access journal PLoS Biology examines the role played by the tumor suppressor protein called p53. It has been found that any mutations of p53 play a key role in the development of many human cancers. //This particular study was carried out by Min Hu, Yigong Shi and colleagues.

To provide a bit of background, when there a cell injury, p53 triggers the activity of several stress-induced genes. In healthy cells, however, p53 levels are controlled by MDM2, a protein that degrades it. Another protein called HAUSP (herpesvirus-associated ubiquitin-specific protease) also plays a role in the regulation of p53's activity by promoting cell death. But HAUSP also plays a key role in destabilizing MDM2. It was this contradictory nature that interested the researchers. They wanted to look at the final sate of p53 after it was regulated by both MSM2 and HAUSP. Hu and his team found that both p53 and MDM2 bind on the same location on HAUSP. They also report that this was possible by conserving a “short amino acid signature" The reseraches arrived at the conclusion that p53-MDM2 pathway is regulated by HAUSP. These findings provide researchers with potential drug-screening targets. By inhibiting HAUSP and consequently MDM2, the tumor promoting mutations could be inhibited.

Main article: Hu M, Gu L, Li M, Jeffrey PD, Gu W, et al. (2006) Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: Implications for the regulation of the P53-MDM2 pathway. PLoS Biol 4(2): e27. LINK: dx.doi.org/10.1371/journal.pbio.0040027
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