Li Muyang, Brooks Christopher L, Wu-Baer Foon, Chen Delin, Baer Richard, Gu Wei
Institute for Cancer Genetics and Department of Pathology, College of Physicians & Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.
Science. 2003 Dec 12;302(5652):1972-5. doi: 10.1126/science.1091362.
Although Mdm2-mediated ubiquitination is essential for both degradation and nuclear export of p53, the molecular basis for the differential effects of Mdm2 remains unknown. Here we show that low levels of Mdm2 activity induce monoubiquitination and nuclear export of p53, whereas high levels promote p53's polyubiquitination and nuclear degradation. A p53-ubiquitin fusion protein that mimics monoubiquitinated p53 was found to accumulate in the cytoplasm in an Mdm2-independent manner, indicating that monoubiquitination is critical for p53 trafficking. These results clarify the nature of ubiquitination-mediated p53 regulation and suggest that distinct mechanisms regulate p53 function in accordance with the levels of Mdm2 activity.
尽管Mdm2介导的泛素化对于p53的降解和核输出均至关重要，但Mdm2产生不同效应的分子基础仍不清楚。在此我们表明，低水平的Mdm2活性诱导p53的单泛素化和核输出，而高水平则促进p53的多泛素化和核降解。一种模拟单泛素化p53的p53-泛素融合蛋白被发现以不依赖Mdm2的方式在细胞质中积累，这表明单泛素化对于p53的转运至关重要。这些结果阐明了泛素化介导的p53调控的本质，并表明不同的机制根据Mdm2活性水平调节p53功能。
