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The amplifier effect: how Pin1 empowers mutant p53

Authors
Journal
Breast Cancer Research
1465-5411
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Volume
13
Issue
5
Identifiers
DOI: 10.1186/bcr2941
Keywords
  • Viewpoint
Disciplines
  • Biology
  • Medicine

Abstract

Mutation of p53 occurs in 15 to 20% of all breast cancers, and with higher frequency in estrogen-receptor negative and high-grade tumors. Certain p53 mutations contribute to malignant transformation not only through loss of wild-type p53 but also through a gain of function of specific p53 mutations. How these hotspot mutations turn p53 from a tumor suppressor into an oncogene had until now remained incompletely understood. In an elegant paper published in the July 12 issue of Cancer Cell, Girardini and colleagues show how Pin1-mediated prolylisomerization, a regulatory mechanism intended by evolution to support p53's function as a guardian of the genome, can go haywire and accelerate malignant transformation when p53 carries a dominant-negative mutation.

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