The amplifier effect: how Pin1 empowers mutant p53.
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 prolyl isomerization, 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.
Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
Hai
H
Hu
Gerburg M
GM
Wulf
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics; D051379:Mice; D009154:Mutation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016159:Tumor Suppressor Protein p53; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse