The tumor suppressor protein p53 is widely implicated in cancer. MDM2, a regulator of cell growth, can inhibit p53 and MDM2-A is one MDM2 splice isoform that is often detected in tumors. Here, Erin Volk, Katja Schuster and colleagues study the role of this truncated protein by creating trans- genic mice that express MDM2-A in normal tissues. Although the mice were not prone to tumor development, heterozygote mice had a shorter life span than wild-type mice and homozygotes died shortly after birth. Studies using MDM2-A mice showed that, in contrast to the cancer-promoting activity of full-length MDM2 protein, MDM2-A activates p53, inhibits growth and enhances cell senescence. This work encourages further exploration of the unique roles of MDM2 variants in tumori-genesis and cell growth.

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