Evidence map›Paper›PMID 22267324›Full record

ArticleMolecular & cellular proteomics : MCP2012

Development of a chemical genetic approach for human aurora B kinase identifies novel substrates of the chromosomal passenger complex.

Rutger C C Hengeveld, Nicholas T Hertz, Martijn J M Vromans, Chao Zhang, Alma L Burlingame, Kevan M Shokat, Susanne M A Lens

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 52 citations in OpenAlex.

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  11. Phospho-regulation of mitotic spindle assembly.Cytoskeleton (Hoboken, N.J.) · 2020
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Rutger C C HengeveldDepartment of Medical Oncology, University Medical Center, 3584 CG Utrecht, The Netherlands.
Nicholas T Hertz
Martijn J M Vromans
Chao Zhang
Alma L Burlingame
Kevan M Shokat
Susanne M A Lens
University Medical Center Utrecht · NLUniversity of California, San Francisco · USUniversity of Southern California · US

Funding

YEAST THREONINE &SERINE KINASESP41RR001614 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 1985 to 2011
$24.1M
RESEARCH TRAINING IN CHEMISTRY AND CHEMICAL BIOLOGYT32GM064337 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2002 to 2021
$7.8M
Bio-Organic Biomedical Mass Spectromy ResourceP41GM103481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURLINGAME, ALMA L · 2012 to 2015
$6.4M
Using chemical genetics to investigate mechanisms of anesthetic actionR01EB001987 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHOKAT, KEVAN M. · 2003 to 2012
$2.9M
PURCHASE OF MICRO LC/NANO ESIQQTOF MASS SPECTROMETERS10RR015804 · NCRR · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI BURLINGAME, ALMA L · 2001 to 2001
$500k
Howard Hughes Medical InstituteNCRR NIH HHS P41 RR001614NCRR NIH HHS S10 RR015804NIBIB NIH HHS R01 EB001987NIBIB NIH HHS R01EB001987NIGMS NIH HHS P41 GM103481NIGMS NIH HHS T32 GM064337PHS HHS NCRR RR001614PHS HHS NCRR RR015804
6 · The paper itself

Abstract

To understand how the chromosomal passenger complex ensures chromosomal stability, it is crucial to identify its substrates and to find ways to specifically inhibit the enzymatic core of the complex, Aurora B. We therefore developed a chemical genetic approach to selectively inhibit human Aurora B. By mutating the gatekeeper residue Leu-154 in the kinase active site, the ATP-binding pocket was enlarged, but kinase function was severely disrupted. A unique second site suppressor mutation was identified that rescued kinase activity in the Leu-154 mutant and allowed the accommodation of bulky N(6)-substituted adenine analogs. Using this analog-sensitive Aurora B kinase, we found that retention of the chromosomal passenger complex at the centromere depends on Aurora B kinase activity. Furthermore, analog-sensitive Aurora B was able to use bulky ATPγS analogs and could thiophosphorylate multiple proteins in cell extracts. Utilizing an unbiased approach for kinase substrate mapping, we identified several novel substrates of Aurora B, including the nucleosomal-binding protein HMGN2. We confirmed that HMGN2 is a bona fide Aurora B substrate in vivo and show that its dynamic association to chromatin is controlled by Aurora B.

Indexed as

Protein Processing, Post-TranslationalAdenosine TriphosphateAmino Acid MotifsAmino Acid SequenceAmino Acid SubstitutionAurora Kinase BAurora KinasesCatalytic DomainCell ExtractsCell Line, TumorCentromereConserved SequenceDiphosphatesHistonesHMGN2 ProteinHumansadenosine 5'-O-(3-thiotriphosphate)Adenosine TriphosphateAURKB protein, humanAurora Kinase BAurora KinasesCell ExtractsDiphosphatesHistonesHMGN2 ProteinLeucineMultiprotein ComplexesPhosphoproteinsProtein Serine-Threonine Kinases

Identifiers

PMID22267324
PMCPMC3418839
OpenAlexW2152142097

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.