Model for regulation of Aurora B by PP1 and I-2 during mitosis. Aurora B is activated by autophosphorylation of T232 in its activation loop, and this reaction can be enhanced by specific binding partners and is reversed by PP1 that inactivates the kinase. Distinct PP1 holoenzymes consist of a catalytic subunit and different regulatory subunits (PP1 R1 and PP1 R2). Different PP1 holoenzymes or PP2A dephosphorylate Aurora B substrates (S1, S2, and S3) to keep the balance of phosphorylation events during different stages of mitosis. Knockdown of I-2 seems equivalent to partial inhibition of Aurora B by indirectly releasing PP1 activity against Aurora B substrates. Conversely, overexpression of I-2 makes cells resistant to partial Aurora B inhibition by hesparadin presumably by inhibiting the counteracting PP1 activity against Aurora B substrates. I-2 binds and inhibits a subset of PP1 holoenzymes (marked by solid inhibition arrow) to regulate phosphorylation of Aurora B substrates. I-2 may also regulate another subset PP1 holoenzymes (marked by dotted inhibition arrow) to regulate Aurora B autophosphorylation.
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