The chromosomal passenger complex activates Polo kinase at centromeres

TY - JOUR

T1 - The chromosomal passenger complex activates Polo kinase at centromeres

AU - Carmena, Mar

AU - Pinson, Xavier

AU - Platani, Melpi

AU - Salloum, Zeina

AU - Xu, Zhenjie

AU - Clark, Anthony

AU - Macisaac, Fiona

AU - Ogawa, Hiromi

AU - Eggert, Ulrike

AU - Glover, David M

AU - Archambault, Vincent

AU - Earnshaw, William C

PY - 2012/1/24

Y1 - 2012/1/24

N2 - The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

AB - The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

KW - Animals

KW - Aurora Kinase B

KW - Aurora Kinases

KW - Cell Culture Techniques

KW - Chromosomal Proteins, Non-Histone

KW - Chromosome Segregation

KW - Drosophila Proteins

KW - Drosophila melanogaster

KW - Enzyme Activation

KW - Gene Expression Regulation, Enzymologic

KW - HeLa Cells

KW - Humans

KW - Kinetochores

KW - Microtubules

KW - Mitosis

KW - Phosphorylation

KW - Protein-Serine-Threonine Kinases

KW - Signal Transduction

KW - Spindle Apparatus

U2 - 10.1371/journal.pbio.1001250

DO - 10.1371/journal.pbio.1001250

M3 - Article

C2 - 22291575

SN - 1544-9173

VL - 10

SP - N/A

JO - PL o S Biology

JF - PL o S Biology

IS - 1

M1 - e1001250

ER -