Wiring the oncogenic circuitry: Pin1 unleashes mutant p53

NAPOLI M.; GIRARDINI J.E.; DEL SAL G.

Oncotarget

Impact Journals

Año: 2011 vol. 2 p. 654 - 656

1949-2553

Unlike several tumor suppressor genes, whose inactivation is due to deletions or truncating mutations, TP53 is most frequently hit by missense mutations in its DNA binding domain. Three are the functional consequences of this single amino acid substitution: i) abrogation of tumor suppressor activities largely due to the inability to recognize wild-type p53 (wtp53) consensus sequences on DNA; ii) inhibition of the tumor suppressor function of the remaining wtp53 allele because of a dominant negative effect; iii) acquisition of new oncogenic properties, commonly described as mutant p53 (mutp53) gain of function, which can actively contribute to various aspects of tumor progression [1]. Intensive research in the last decade has definitively confirmed that mutp53 promotes the development of aggressive tumors, characterized by a metastatic phenotype and high levels of genomic instability [2-4]. Elegant in vivo studies have suggested that mutp53 requires additional alterations to exert its gain of function activities. Indeed, these properties were shown to be associated with mutp53 phosphorylation, suggesting that efficient mutp53 function may be triggered by oncogenic signaling, similarly to what occurs in the case of wtp53 [4, 5]. Very recently, we have unveiled a crucial link between cancer-related signaling and mutp53 oncogenic function: the prolyl isomerase Pin1, which transduces proline-directed signaling into mutp53 activation [5].