[摘要]：The proteasome activator REG gamma mediates a shortcut for the destruction of intact mammalian proteins. The biological roles of REG gamma and the underlying mechanisms are not fully understood. Here we provide evidence that REG gamma regulates cellular distribution of p53 by facilitating its multiple monoubiquitylation and subsequent nuclear export and degradation. We also show that inhibition of p53 tetramerization by REG gamma might further enhance cytoplasmic relocation of p53 and reduce active p53 in the nucleus. Furthermore, multiple monoubiquitylation of p53 enhances its physical interaction with HDM2 and probably facilitates subsequent polyubiquitylation of p53, suggesting that monoubiquitylation can act as a signal for p53 degradation. Depletion of REG gamma sensitizes cells to stress-induced apoptosis, validating its crucial role in the control of apoptosis, probably through regulation of p53 function. Using a mouse xenograft model, we show that REG gamma knockdown results in a significant reduction of tumor growth, suggesting an important role for REG gamma in tumor development. Our study therefore demonstrates that REG gamma-mediated inactivation of p53 is one of the mechanisms involved in cancer progression.
