原卟啉 IX 对 p53 和其同源物 p73 的靶向作用。
Targeting of p53 and its homolog p73 by protoporphyrin IX.
机构信息
Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk & Medical University of Gdansk, Gdansk, Poland.
出版信息
FEBS Lett. 2011 Jan 3;585(1):255-60. doi: 10.1016/j.febslet.2010.12.004. Epub 2010 Dec 10.
The p53 tumor suppressor is recognized as a promising target for anti-cancer therapies. We previously reported that protoporphyrin IX (PpIX) disrupts the p53/murine double minute 2 (MDM2) complex and leads to p53 accumulation and activation of apoptosis in HCT 116 cells. Here we show the direct binding of PpIX to the N-terminal domain of p53. Furthermore, we addressed the induction of apoptosis in HCT 116 p53-null cells by PpIX and revealed interactions between PpIX and p73. We propose that PpIX disrupts the p53/MDM2 or MDMX and p73/MDM2 complexes and thereby activates the p53- or p73-dependent cancer cell death.
抑癌基因 p53 被认为是癌症治疗的一个有前途的靶点。我们之前的研究表明原卟啉 IX（PpIX）可以破坏 p53/鼠双微体 2（MDM2）复合物，导致 HCT 116 细胞中 p53 积累和凋亡激活。在这里，我们展示了 PpIX 与 p53 的 N 端结构域的直接结合。此外，我们还研究了 PpIX 诱导 HCT 116 p53 缺失细胞凋亡的情况，并揭示了 PpIX 与 p73 之间的相互作用。我们提出，PpIX 破坏 p53/MDM2 或 MDMX 和 p73/MDM2 复合物，从而激活 p53 或 p73 依赖性的癌细胞死亡。
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