Survivin mutant (Surv-DD70, 71AA) disrupts the interaction of Survivin with Aurora B and causes multinucleation in HeLa cells.
Survivin is associated with Aurora B, inner centromere protein (INCENP), and borealin to form a chromosomal passenger complex that plays multiple roles during cell division. We used mutational analysis to study interaction of Survivin with Aurora B and the effect of this interaction on cell division. A Survivin mutant with the terminal domain deleted (Survivin 1-107) bound Aurora B as efficiently as Survivin wild type. This indicated that the proximal BIR domain of Survivin was responsible for Survivin binding to Aurora B. Survivin mutants (Surv-R18A, Surv-D53A, and Sur-KK78, and 79AA) all bound to Aurora B efficiently, but mutation in the conserved amino acid residues of the acidic patch on Survivin (Surv-DD70, 71AA) abolished the direct interaction of Survivin and Aurora B. The Survivin mutant (Surv-DD70, 71AA) localized diffusely in metaphase and failed to successfully accumulate in the midbody during cytokinesis. Furthermore, over-expression of the Survivin mutant (Surv-DD70, 71AA) severely disturbed cytokinesis, resulting in multinucleation in HeLa cell. This indicated that the direct interaction of Survivin and Aurora B was critical for the correct location of Survivin and the function of the Survivin complex in cell division.
Cao
Lihuan
L
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, PR China.
Yan
Xiaomei
X
Wu
Yanhua
Y
Hu
Hairong
H
Li
Qiang
Q
Zhou
Tong
T
Jiang
Songmin
S
Yu
Long
L
D000595:Amino Acid Sequence; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002467:Cell Nucleus / Q000502:physiology*; D048749:Cytokinesis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008677:Metaphase / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases