Evidence map›Paper›PMID 23829974›Full record

ArticleEpigenetics & chromatin2013

Functional impact of Aurora A-mediated phosphorylation of HP1γ at serine 83 during cell cycle progression.

Adrienne Grzenda, Phoebe Leonard, Seungmae Seo, Angela J Mathison, Guillermo Urrutia, Ezequiel Calvo, Juan Iovanna, Raul Urrutia, Gwen Lomberk

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

17 citing papers in PubMed, 24 citations in OpenAlex.

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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

9 authors at 3 institutions in 3 countries.

Adrienne GrzendaLaboratory of Epigenetics and Chromatin Dynamics, GIH Division, Department of Medicine, Biochemistry and Molecular Biology, Guggenheim 10, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. lomberk.gwen@mayo.edu.
Phoebe Leonard
Seungmae Seo
Angela J Mathison
Guillermo Urrutia
Ezequiel Calvo
Juan Iovanna
Raul Urrutia
Gwen Lomberk
Mayo Clinic · USCentre hospitalier de l'Université Laval · CAInserm · FR

Funding

Tissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI MUKHOPADHYAY, DEBABRATA · 2004 to 2018
$32.7M
PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI Samar Ibrahim · 2009 to 2026
$22.2M
ZINC FINGER GENES AND PANCREATIC CELL GROWTHR01DK052913 · NIDDK · MEDICAL COLLEGE OF WISCONSIN · PI LOMBERK, GWEN, URRUTIA, RAUL A. · 1998 to 2023
$7.0M
Novel Experimental Therapeutics for Pancreatic CancerR01CA178627 · NCI · MEDICAL COLLEGE OF WISCONSIN · PI LOMBERK, GWEN · 2014 to 2018
$1.6M
Tumor Microenvironment/Angiogenesis Training GrantT32CA148073 · NCI · MAYO CLINIC ROCHESTER · PI MC NIVEN, MARK A. · 2010 to 2014
$1.2M
NCI NIH HHS P50 CA102701NCI NIH HHS R01 CA178627NCI NIH HHS T32 CA148073NIDDK NIH HHS P30 DK084567NIDDK NIH HHS R01 DK052913
6 · The paper itself

Abstract

backgroundPrevious elegant studies performed in the fission yeast Schizosaccharomyces pombe have identified a requirement for heterochromatin protein 1 (HP1) for spindle pole formation and appropriate cell division. In mammalian cells, HP1γ has been implicated in both somatic and germ cell proliferation. High levels of HP1γ protein associate with enhanced cell proliferation and oncogenesis, while its genetic inactivation results in meiotic and mitotic failure. However, the regulation of HP1γ by kinases, critical for supporting mitotic progression, remains to be fully characterized.

resultsWe report for the first time that during mitotic cell division, HP1γ colocalizes and is phosphorylated at serine 83 (Ser83) in G2/M phase by Aurora A. Since Aurora A regulates both cell proliferation and mitotic aberrations, we evaluated the role of HP1γ in the regulation of these phenomena using siRNA-mediated knockdown, as well as phosphomimetic and nonphosphorylatable site-directed mutants. We found that genetic downregulation of HP1γ, which decreases the levels of phosphorylation of HP1γ at Ser83 (P-Ser83-HP1γ), results in mitotic aberrations that can be rescued by reintroducing wild type HP1γ, but not the nonphosphorylatable S83A-HP1γ mutant. In addition, proliferation assays showed that the phosphomimetic S83D-HP1γ increases 5-ethynyl-2´-deoxyuridine (EdU) incorporation, whereas the nonphosphorylatable S83A-HP1γ mutant abrogates this effect. Genome-wide expression profiling revealed that the effects of these mutants on mitotic functions are congruently reflected in G2/M gene expression networks in a manner that mimics the on and off states for P-Ser83-HP1γ.

conclusionsThis is the first description of a mitotic Aurora A-HP1γ pathway, whose integrity is necessary for the execution of proper somatic cell division, providing insight into specific types of posttranslational modifications that associate to distinct functional outcomes of this important chromatin protein.

Identifiers

PMID23829974
PMCPMC3707784
OpenAlexW2162100602

What OpenQuestion holds

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Registered trials

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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.