PXD006892

PXD006892 is an original dataset announced via ProteomeXchange.

Title	Aurora A kinase phosphorylates Hec1 to regulate metaphase kinetochore-microtubule dynamics.
Description	Precise regulation of kinetochore-microtubules is essential for successful chromosome segregation. Central to this regulation is Aurora B kinase, which phosphorylates kinetochore substrates to promote microtubule turnover. A critical target of Aurora B is the N-terminal “tail” domain of Hec1/NDC80, which is a component of the NDC80 complex, a force-transducing link between kinetochores and microtubules. While Aurora B is regarded as the “master regulator” of kinetochore-microtubule attachment, it is likely that other mitotic kinases contribute to Hec1phosphorylation. Here we show that Aurora A kinase phosphorylates the tail domain of Hec1 at Serine 69, a previously uncharacterized phosphorylation target site, and plays an important role in controlling kinetochore-microtubule attachment dynamics. Using phospho-specific antibodies, Hec1 phospho-deficient mutants, and kinase inhibitors, we demonstrate that Aurora A is required for the regulation of kinetochore-microtubule dynamics of metaphase chromosomes and identify Hec1 Serine 69 as a critical Aurora A substrate for this regulation. Additionally, we demonstrate that Aurora A kinase associates with INCENP during mitosis and that INCENP is competent to drive accumulation of the kinase to the centromere region of mitotic chromosomes. These findings reveal that both Aurora A and Aurora B contribute to kinetochore-microtubule attachment dynamics, and they uncover an unexpected role for Aurora A in mitosis.
HostingRepository	PRIDE
AnnounceDate	2017-11-28
AnnouncementXML	Submission_2017-12-11_03:56:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-07 01:57:26	ID requested
1	2017-11-28 03:50:44	announced
⏵ 2	2017-12-11 03:56:16	announced	Updated publication reference for PubMed record(s): 29187526.

DeLuca KF, Meppelink A, Broad AJ, Mick JE, Peersen OB, Pektas S, Lens SMA, DeLuca JG, Aurora A kinase phosphorylates Hec1 to regulate metaphase kinetochore-microtubule dynamics. J Cell Biol, 217(1):163-177(2018) [pubmed]

curator keyword: Biological

submitter keyword: human Aurora A kinase Hec1

Susanne Lens
contact affiliation	Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
contact email	S.M.A.Lens@umcutrecht.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/11/PXD006892

PRIDE project URI

• PRIDE
  1. PXD006892
     1. Label: PRIDE project
     2. Name: Aurora A kinase phosphorylates Hec1 to regulate metaphase kinetochore-microtubule dynamics.