Tumor protein p53, a nuclear protein, plays an essential role in the regulation of cell cycle, specifically in the transition from G0 to G1. It is found in very low levels in normal cells, however, in a variety of transformed cell lines, it is expressed in high amounts, and believed to contribute to transformation and malignancy. P53 is subject to modification by conjugation of SUMO-1. A p53 mutant deficient for MDM2 binding is poorly sumoylated in vivo compared to wild-type p53. Overexpression of MDM2 increases the level of p53 sumoylation, which is further stimulated by expression of ARF. These results show that p53 sumoylation is regulated by MDM2- and ARF-mediated nucleolar targeting.

HUMAN

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