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PMID:28751710
Citation |
Shrestha, RL, Conti, D, Tamura, N, Braun, D, Ramalingam, RA, Cieslinski, K, Ries, J and Draviam, VM (2017) Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells. Nat Commun 8:150 |
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Abstract |
Human chromosomes are captured along microtubule walls (lateral attachment) and then tethered to microtubule-ends (end-on attachment) through a multi-step end-on conversion process. Upstream regulators that orchestrate this remarkable change in the plane of kinetochore-microtubule attachment in human cells are not known. By tracking kinetochore movements and using kinetochore markers specific to attachment status, we reveal a spatially defined role for Aurora-B kinase in retarding the end-on conversion process. To understand how Aurora-B activity is counteracted, we compare the roles of two outer-kinetochore bound phosphatases and find that BubR1-associated PP2A, unlike KNL1-associated PP1, plays a significant role in end-on conversion. Finally, we uncover a novel role for Aurora-B regulated Astrin-SKAP complex in ensuring the correct plane of kinetochore-microtubule attachment. Thus, we identify Aurora-B as a key upstream regulator of end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process.Human chromosomes are captured along microtubule walls and then tethered to microtubule-ends through a multi-step end-on conversion process. Here the authors show that Aurora-B regulates end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process. |
Links |
PubMed PMC5532248 Online version:10.1038/s41467-017-00209-z |
Keywords |
Aurora Kinase B/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; HeLa Cells; Humans; Immunoblotting; Kinetochores/metabolism; Microscopy, Fluorescence; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Microtubules/metabolism; Phosphoric Monoester Hydrolases/metabolism; Protein Binding; RNA Interference; Signal Transduction; Time-Lapse Imaging/methods |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
GO:0004674: protein serine/threonine kinase activity |
ECO:0000314: |
F |
Fig. 1 shows that in human cells, Aurora-B (Aurora Kinase B, AURKB) is responsible for phosphorylation of serine residues on the kinetochore HEC1 protein. |
complete | ||||
GO:1905116: positive regulation of lateral attachment of mitotic spindle microtubules to kinetochore |
ECO:0000314: |
P |
Fig. 1 shows that in human cells, Aurora-B (Aurora Kinase B, AURKB) is very active on lateral kinetochores and that this activity promotes association of kinetochores and microtubules. |
complete | ||||
Notes
Scavenger Hunt - 3
See also
References
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