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Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells
Jun Chen1, Sha Jin, Stephen K Tahir
1Abbott Laboratories, Cancer Research, AP10-1, Abbott Park, Illinois 60064, USA. jun.chen@abbott.com
Abstract:
Survivin, one of the most tumor-specific gene products, has been implicated in both anti-apoptosis and cytokinesis. However, the mechanism by which survivin regulates these two different processes is still elusive. Here, we show that survivin binds to the catalytic domain of Aurora-B. We demonstrate that in the presence of survivin, Aurora-B phosphorylates histone H3 much more efficiently than in the absence of survivin in a cell-free system. Furthermore, we confirm that cells lacking survivin due to survivin antisense oligonucleotide-treatment have lower Aurora-B kinase activity, whereas cells overexpressing survivin have higher Aurora-B kinase activity. We also provide evidence that depletion of survivin by survivin antisense oligonucleotide treatment causes significant reduction of endogenous phosphorylated histone H3 and mislocalization of Aurora-B. These results indicate that survivin stimulates Aurora-B kinase activity and helps correctly target Aurora-B to its substrates during the cell cycle, thus providing a mechanism as to how survivin exerts its function in human cells.
Insights
Survivin protein enhances Aurora-B kinase activity and ensures its proper cellular localization. This study reveals survivin
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Survivin is a key protein involved in tumor suppression and cell division.
- The precise mechanisms by which survivin regulates anti-apoptosis and cytokinesis remain unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of survivin's function in cellular processes.
- To investigate the interaction between survivin and Aurora-B kinase.
Main Methods:
- In vitro binding assays to confirm survivin-Aurora-B interaction.
- Kinase assays using cell-free systems to measure Aurora-B activity.
- Antisense oligonucleotide treatment to deplete survivin levels in cells.
- Western blotting to assess levels of phosphorylated histone H3 and Aurora-B localization.
Main Results:
- Survivin directly binds to the catalytic domain of Aurora-B.
- Survivin significantly enhances Aurora-B's ability to phosphorylate histone H3.
- Depletion of survivin reduces Aurora-B kinase activity and causes its mislocalization.
- Overexpression of survivin increases Aurora-B kinase activity.
Conclusions:
- Survivin acts as a crucial stimulator of Aurora-B kinase activity.
- Survivin facilitates the correct targeting of Aurora-B to its substrates during the cell cycle.
- This interaction provides a mechanistic explanation for survivin's roles in human cells.