Page 194 - ebook

[B. Cell Biology/Stem Cell] B-32

Spatiotemporal Coordination of the RSF1-PLK1-Aurora B

Cascade Establishes Mitotic Signaling Platforms

#
#
Ho-Soo Lee¹ *, Sunwoo Min¹ , Ye-Eun Jung², June Heo¹,³, Sun-Shin Cha², Hyeseong Cho¹*
¹Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea, ²Chemistry &

Nanoscience, Ewha Womans University, Seoul 03760, Korea, ³Biomedical Sciences, Graduate School of Ajou

University, Suwon 16499, Korea

The chromatin remodeler RSF1 enriched at mitotic centromeres is essential for proper chromosome alignment and
segregation and underlying mechanisms remain to be disclosed. We here show that PLK1 recruitment by RSF1 at

centromeres creates an activating phosphorylation on Thr236 in the activation loop of Aurora B and this is
indispensable for the Aurora B activation. In structural modeling the phosphorylated Thr236 enhances the base-

catalysis by Asp200 nearby, facilitating the Thr232 autophosphorylation. Accordingly, RSF1-PLK1 is central for Aurora
B-mediated microtubule destabilization in error correction. However, under full microtubule-kinetochore attachment

RSF1-PLK1 positions at kinetochores, halts activating Aurora B and phosphorylates BubR1, regardless of tension.
Spatial movement of RSF1-PLK1 to kinetochores is triggered by Aurora B-mediated phosphorylation of centromeric

histone H3 on Ser28. We propose a regulatory RSF1-PLK1 axis that spatiotemporally controls on/off switch on
Aurora B. This feedback circuit among RSF1-PLK1-Aurora B may coordinate dynamic microtubule-kinetochore

attachment in early mitosis when full tension yet to be generated