中文摘要：

肿瘤 suppressor p53 在细胞生长或 apoptosis 平衡的关键点定位，并且 p53 的表示水平是紧包括 MDM2 由 ubiquitin ligases 控制了。在 DNA 损坏压力之上， p53 被积累并且激活，导致房间周期拘捕或 apoptosis。我们以前显示出规章的因素 1/2 (Smurf1/2 ) 支持的那 Smad ubiquitylation 由交往与并且稳定 MDM2，并且因而提高 p53 的调停 MDM2 的 ubiquitylation 的 p53 降级。然而， Smurf1-MDM2 相互作用怎么响应 DNA 损坏应力被调整，是不清楚的。这里，我们证明响应 etoposide 处理， Smurf1 从 MDM2 分裂，导致 MDM2 destabilization 和 p53 累积。apoptosis 上的 Smurf1 的否定规定被释放。尤其是，这分离是一个慢过程而非快速的回答，高含有 Smurf1 的表示可能对 p53 激活授与抵抗。与这个观点一致，我们观察到 Smurf1/2 ligases 高度在结肠癌，食道的有鳞的房间癌和胰腺的癌症纸巾被表示，建议 Smurf1/2 的 oncogenic 趋势。

英文摘要：

The tumor suppressor p53 locates at the key point of cell growth or apoptosis balance, and the expression level of p53 is tightly controlled by ubiquitin ligases including MDM2. Upon DNA damage stresses, p53 was accumulated and activated, leading to cell cycle arrest or apoptosis. We previously showed that Smad ubiquitylation regulatory factor 1/2 （Smurfl/2） promotes p53 degradation by interacting with and stabilizing MDM2, and consequently enhancing MDM2-mediated ubiquitylation of p53. However, it is unclear how the Smurfl-MDM2 interaction is regulated in response to DNA damage stress. Here, we show that in response to etoposide treatment Smurfl dissociates from MDM2, resulting in MDM2 destabilization and p53 accumulation. The negative regulation of Smurfl on apoptosis is released. Notably, this dissociation is a slow process rather than a rapid response, implicating high expression of Smurfl might confer the resistance against p53 activation. Consistent with this notion, we observed that Smurfl/2 ligases are highly expressed in colon cancer, esophageal squamous cell carcinoma and pancreatic cancer tissues, suggesting the oncogenic tendency of Smurfl/2.