Survivin is a cancer-associated protein regulated by multiple factors, including acetylation at K129 within its C-terminal α-helical tail. Acetylation of survivin is being pursued as a potential prognostic marker in breast cancer. This modification at K129 may cause nuclear accumulation of survivin in interphase cells; however, whether this affects its essential role during mitosis has not been addressed. We posited whether mimicking acetylation of survivin at K129 alters its activity during mitosis. Fluorescence microscopy and time-lapse imaging showed that, mutating this site to an alanine to act as a constitutive acetyl mimetic, K129A, causes defects in chromosome segregation and cytokinesis. As a non-acetylatable version, K129R, also has difficulty during mitotic exit, we conclude that cyclical acetylation and deacetylation is required for fully functional survivin during mitosis.
Keywords: CHX, cycloheximide; CPC, chromosomal passenger complex; CPP, chromosomal passenger protein; DMA, dimethylenastron; IAP, inhibitor of apoptosis; NES, nuclear exportation signal; PTM, post-translational modification; SAC, spindle assembly checkpoint; SVN, survivin; TRAIL, Tumor-necrosis factor Responsive Apoptosis Inducing Ligand; TSA, Trichostatin A; WT, wild type; acetylation; apoptosis; cancer; mitosis; survivin.