Department of Molecular Cell Biology, The Weizmann Institute, Rehovot 76100, Israel.
Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a001107. doi: 10.1101/cshperspect.a001107.
In its wild-type form, p53 is a major tumor suppressor whose function is critical for protection against cancer. Many human tumors carry missense mutations in the TP53 gene, encoding p53. Typically, the affected tumor cells accumulate excessive amounts of the mutant p53 protein. Various lines of evidence indicate that, in addition to abrogating the tumor suppressor functions of wild-type p53, the common types of cancer-associated p53 mutations also endow the mutant protein with new activities that can contribute actively to various stages of tumor progression and to increased resistance to anticancer treatments. Collectively, these activities are referred to as mutant p53 gain-of-function. This article addresses the biological manifestations of mutant p53 gain-of-function, the underlying molecular mechanisms, and their possible clinical implications.
在野生型形式中，p53 是一种主要的肿瘤抑制因子，其功能对于预防癌症至关重要。许多人类肿瘤在编码 p53 的 TP53 基因中携带错义突变。通常，受影响的肿瘤细胞会积累过量的突变型 p53 蛋白。各种证据表明，除了消除野生型 p53 的肿瘤抑制功能外，常见类型的癌症相关 p53 突变还赋予突变蛋白新的活性，这些活性可积极促进肿瘤进展的各个阶段，并增加对癌症治疗的抵抗力。这些活性统称为突变型 p53 获得功能。本文探讨了突变型 p53 获得功能的生物学表现、潜在的分子机制及其可能的临床意义。
