Molecular Oncology Department, Moffitt Cancer Center; Tampa, FL USA.
Cell Cycle. 2011 Apr 1;10(7):1162-6. doi: 10.4161/cc.10.7.15249.
It is widely accepted that DNA damage induces rapid degradation of MDM2 through phosphorylation, resulting in a transient reduction of MDM2 level. Elimination of MDM2 is a logical mechanism that stabilizes p53. This phenomenon has been reproduced by many independent studies and is frequently referenced. Here we present evidence that only phosphorylation-sensitive antibodies SMP14 and 2A10, but not other MDM2 antibodies, can detect robust down-regulation of MDM2 after DNA damage. Therefore, we conclude that DNA damage does not accelerate MDM2 auto-degradation. SMP14 and 2A10 are frequently used to detect human and mouse MDM2, respectively. While it is not clear whether the discrepancy is entirely due to the use of these antibodies, our results suggest that epitope masking by phosphorylation should be an important consideration when interpreting results of MDM2 analysis by SMP14 and 2A10.
人们普遍认为，DNA 损伤通过磷酸化诱导 MDM2 的快速降解，导致 MDM2 水平的短暂降低。消除 MDM2 是稳定 p53 的合理机制。这一现象已被许多独立的研究重现，并经常被引用。在这里，我们提供的证据表明，只有磷酸化敏感的抗体 SMP14 和 2A10，但不是其他的 MDM2 抗体，可以检测到 DNA 损伤后 MDM2 的显著下调。因此，我们得出结论，DNA 损伤不会加速 MDM2 的自动降解。SMP14 和 2A10 分别常用于检测人和鼠的 MDM2。虽然尚不清楚这种差异是否完全归因于这些抗体的使用，但我们的结果表明，当使用 SMP14 和 2A10 分析 MDM2 时，磷酸化引起的表位掩盖应该是一个重要的考虑因素。
