Mitotic activity of survivin is regulated by acetylation at K129.
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.
a School of Life Sciences; University of Nottingham; Queen's Medical Centre ; Nottingham , UK.
Aysha M
AM
Aljaberi
Jamie Rm
JR
Webster
Sally P
SP
Wheatley
D000107:Acetylation; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D020125:Mutation, Missense / Q000235:genetics; D000077022:Survivin; D059008:Time-Lapse Imaging
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin
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