Mitotic activity of survivin is regulated by acetylation at K129

作者：Aljaberi Aysha M; Webster Jamie R M; Wheatley Sally P^*

来源：Cell Cycle, 2015, 14(11): 1738-1747.

DOI：10.1080/15384101.2015.1033597

• apoptosis
• survivin
• mitosis
• cancer
• acetylation
• CHX, cycloheximide
• CPC, chromosomal passenger complex
• TRAIL, Tumor-necrosis factor Responsive Apoptosis Inducing Ligand
• WT, wild type
• IAP, inhibitor of apoptosis
• CPP, chromosomal passenger protein
• TSA, Trichostatin A
• SVN, survivin
• SAC, spindle assembly checkpoint
• PTM, post-translational modification
• NES, nuclear exportation signal
• DMA, dimethylenastron

Survivin is a cancer-associated protein regulated by multiple factors, including acetylation at K129 within its C-terminal alpha-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.

• 出版日期2015-6-3