Liaisons between survivin and Plk1 during cell division and cell death

Area of Science:

• Cell Biology
• Molecular Oncology
• Biochemistry

Background:

• Survivin and Plk1 kinase are key regulators of cell survival, mitosis, and apoptosis.
• Both proteins are frequently deregulated in various cancers.
• Similarities in their functions suggest a potential cooperative role in cell division and death pathways.

Purpose of the Study:

• To investigate the interaction between survivin and Plk1 kinase during mitosis.
• To determine the functional significance of survivin phosphorylation by Plk1 at serine 20.
• To elucidate the role of this specific phosphorylation event in chromosome alignment, cell cycle progression, and apoptosis.

Main Methods:

• Co-immunoprecipitation to detect survivin-Plk1 interaction.
• Site-directed mutagenesis to create non-phosphorylatable (S20A) and phosphomimic (S20D) survivin mutants.
• Analysis of chromosome alignment, spindle checkpoint function, and cell proliferation using microscopy and cell culture assays.
• Assessment of anti-apoptotic activity in response to TRAIL stimulation.

Main Results:

• Survivin and Plk1 interact during mitosis, with Plk1 phosphorylating survivin at serine 20.
• Overexpression of the S20A mutant impairs chromosome alignment and allows cells to bypass the spindle tension checkpoint.
• The S20D phosphomimic mutant supports cell proliferation, unlike the S20A mutant.
• Phosphorylation at Ser20 is critical for mitosis but does not affect survivin's anti-apoptotic role against TRAIL.

Conclusions:

• Plk1-mediated phosphorylation of survivin at Ser20 is essential for proper chromosome alignment and cell proliferation during mitosis.
• This phosphorylation event is separable from survivin's anti-apoptotic function.
• Targeting the survivin-Plk1 interaction or survivin phosphorylation could be a therapeutic strategy in cancer, focusing on mitotic disruption rather than apoptosis induction.