title: B56-PP2A regulates motor dynamics for mitotic chromosome alignment.
abstract: Proper alignment of duplicated chromosomes at the metaphase plate involves both motor-driven chromosome movement and the functional and physical end-on connection (K-fiber formation) between the kinetochore and the plus-end of microtubules. The B56 family of protein phosphatase 2A (PP2A) regulatory subunits (B56-PP2A), through their interaction with the mitotic checkpoint protein BUBR1, are required for proper chromosome alignment, but the underlying mechanism(s) has remained elusive. Here, we show that B56-PP2A promotes chromosome alignment primarily by balancing chromosome movement towards the metaphase plate, rather than by directly establishing stable K-fibers. Notably, the poleward movement of chromosomes in cells depleted of the B56 family can be rescued by depletion of HSET (also known as kinesin-14 or KIFC1), a major minus-end-directed motor protein. Strikingly, K-fiber formation can be restored if chromosome movement to the metaphase plate is rescued in B56-depleted cells. Furthermore, the B56-BUBR1 interaction is required for promoting motor-driven chromosome movement towards the metaphase plate. Thus, we propose that B56-PP2A functions in mitotic chromosome alignment by balancing chromosome movement towards the metaphase plate, which is essential for the subsequent establishment of stable and functional kinetochore-microtubule attachments, and mitotic exit.
authors.affiliation: Program in Cancer & Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, 8 College Road, Singapore 169857, Singapore NUS Graduate School for Integrative Sciences and Engineering, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Program in Cancer & Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, 8 College Road, Singapore 169857, Singapore.
authors.forename: David M
authors.initials: DM
authors.lastname: Virshup
authors.affiliation: Program in Cancer & Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, 8 College Road, Singapore 169857, Singapore sanghyun.lee@duke-nus.edu.sg.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Lee
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C486566:KIFC1 protein, human; C525690:PPP2R5A protein, human; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2; D016547:Kinesins
keywords: BUBR1; Chromosome congression; Kinesin; Mitosis; PP2A