Long overshadowed by p53, its famous tumor-suppressing sibling, the p63 gene does the tougher, important job of stifling the spread of cancer to other organs. Not only does a specific form of p63 protein block metastasis, but it does so by activating the enzyme Dicer, which plays a pivotal role in the creation of microRNAs.
Researchers at MD Anderson Cancer Center show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Additionally, modulation of expression of Dicer and miR-130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63.
These data provide a novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b and may have implications for the many processes regulated by miRNAs.
Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB, Wistuba I, Flores ER (2010) TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 467, 986–990. [abstract]