Research

apoptinaApoptin is a small protein from the chicken anemia virus‎ which selectively induces apoptosis (programmed cell suicide) in over 80 different cancer cell lines, yet does not harm healthy cells. Apoptin is a promising cancer lead and is progressing through clinical trials. Nevertheless, Apoptin's strong tendency to oligomerize limits its ability to enter cells and thwarts studies of its structure. Therefore, we have prepared and characterized a monomeric Apoptin variant that retains most of the wild type protein's selective anti-cancer activity. Using NMR spectroscopy, this variant was shown to be intrinsically disordered and dynamic on ps-ms time scales. The conformational ensemble is not significantly affected by specific phosphorylation, addition of Mg++, pH changes or red/ox conditions. These findings support a model for Apoptin's mechanism of action in which cancer specific kinases phosphorylate Apoptin, leading to its accumulation in the nucleus and activation of p53-independent apoptosis.

Referencias:

1. "Insights into the mechanism of Apoptin's exquisitely selective anti-tumor action from atomic level characterization of its conformation and dynamics." Ruiz-Martínez S, Pantoja-Uceda D, Castro J, Vilanova M, Ribó M, Bruix M, Benito A, Laurents DV. Arch Biochem Biophys. (2017) 614:53-64.
doi:10.1016/j.abb.2016.12.010

2. "A truncated Apoptin protein variant selectively kills cancer cells." Ruiz-Martínez S, Castro J, Vilanova M, Bruix M, Laurents DV, Ribó M, Benito A. Invest New Drugs (2017).
doi:10.1007/s10637-017-0431-6