INCENP-aurora B interactions modulate kinase activity and chromosome passenger complex localization

Area of Science:

• Cell Biology
• Molecular Biology
• Mitosis Regulation

Background:

• Dynamic localization of the chromosomal passenger complex (CPC) during mitosis is crucial for its functions.
• CPC centromere targeting involves interactions between Survivin, Borealin, and the inner centromere protein (INCENP) N terminus.

Purpose of the Study:

• To investigate how INCENP C-terminal interactions with aurora B kinase modulate kinase activity levels.
• To determine the impact of varying kinase activity on CPC localization and mitotic functions.

Main Methods:

• Studied INCENP-depleted cells and cells expressing INCENP mutants with altered aurora B binding or activation.
• Assessed spindle checkpoint response under varying microtubule conditions (absent or low-dose taxol).
• Monitored CPC transfer from chromosomes to the anaphase spindle midzone.

Main Results:

• Low aurora B kinase activity (INCENP-depleted or non-binding mutants) supported spindle checkpoint without microtubules but failed against low-dose taxol.
• Intermediate kinase activity (mutant binding but not fully activating aurora B) enabled robust taxol response but not CPC transfer to the midzone.
• CPC transfer to the anaphase spindle midzone required significantly higher aurora B activity levels.

Conclusions:

• INCENP interactions with aurora B in vivo precisely modulate kinase activity.
• Modulated kinase activity by INCENP dictates CPC localization dynamics and mitotic functions.
• Differential aurora B activity levels fine-tune CPC's roles throughout mitosis.