Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell Death Differ. 2010 Jan;17(1):103-8. doi: 10.1038/cdd.2009.67.
The mechanism of p53 proteasomal degradation through polyubiquitination is well characterized. The basic assumption behind this mechanism is that p53 is inherently stable unless sensitized to degradation by polyubiquitination. However, a number of studies provide evidence for p53 to be naturally unstable. Consistent with this attribute is the fact that both p53 N- and C-termini are intrinsically unstructured. Recent findings provide evidence for p53 to be degraded by the 20S proteasome by default unless it escapes this process. A number of mechanisms were demonstrated and proposed to play a role in rescuing p53 from default degradation. These mechanisms, their biological implications, and relevance to cancer are reviewed in this article.
通过多泛素化实现 p53 蛋白体降解的机制已得到充分研究。该机制背后的基本假设是，p53 本身是稳定的，除非通过多泛素化被敏化而导致降解。然而，许多研究提供了证据表明 p53 天然不稳定。与这一特性一致的是，p53 的 N 端和 C 端都是内在无结构的。最近的研究结果表明，p53 除非逃脱这个过程，否则会被 20S 蛋白酶体默认降解。许多机制已被证明并被提出在 p53 从默认降解中被拯救中发挥作用。本文综述了这些机制及其生物学意义以及与癌症的相关性。
