Evidence map›Paper›PMID 24710275›Full record

ArticleMolecular and cellular biology2014

Loss of the mammalian DREAM complex deregulates chondrocyte proliferation.

Chantal Forristal, Shauna A Henley, James I MacDonald, Jason R Bush, Carley Ort, Daniel T Passos, Srikanth Talluri, Charles A Ishak, Michael J Thwaites, Chris J Norley and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

22 citing papers in PubMed, 37 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

16 authors at 4 institutions in 2 countries.

Chantal ForristalLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada.
Shauna A HenleyLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada.
James I MacDonaldLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada.
Jason R BushChildren's Health Research Institute, Western University, London, Ontario, Canada Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.
Carley OrtDepartment of Physiology and Pharmacology, Western University, London, Ontario, Canada.
Daniel T PassosLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada.
Srikanth TalluriLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada.
Charles A IshakLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada.
Michael J ThwaitesLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada.
Chris J NorleyDepartment of Medical Biophysics, Western University, London, Ontario, Canada.
Larisa LitovchickDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
James A DeCaprioDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Gabriel DiMattiaLondon Regional Cancer Program, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada Department of Oncology, Western University, London, Ontario, Canada.
David W HoldsworthDepartment of Medical Biophysics, Western University, London, Ontario, Canada.
Frank BeierChildren's Health Research Institute, Western University, London, Ontario, Canada Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.
Frederick A DickLondon Regional Cancer Program, Western University, London, Ontario, Canada Children's Health Research Institute, Western University, London, Ontario, Canada Department of Biochemistry, Western University, London, Ontario, Canada Department of Oncology, Western University, London, Ontario, Canada fdick@uwo.ca.
Western University · CABrigham and Women's Hospital · USChildren’s Health Research Institute · CAVirginia Commonwealth University · US

Funding

RB-RELATED PROTEINS IN SV4OT AND E1A TRANSFORMATIONR01CA063113 · NCI · DANA-FARBER CANCER INSTITUTE · PI DECAPRIO, JAMES A. · 1994 to 2018
$5.0M
CIHR MOP43899NCI NIH HHS R01 CA063113
6 · The paper itself

Abstract

Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes.

Indexed as

Amino Acid SequenceAnimalsAnimals, NewbornCell CycleCell ProliferationChondrocytesEmbryo, MammalianFibroblastsGene Expression RegulationHarmineHumansMammalsMiceMice, Mutant StrainsModels, AnimalMolecular Sequence DataHarmineMultiprotein ComplexesRetinoblastoma Protein

Identifiers

PMID24710275
PMCPMC4054284
OpenAlexW2138140953

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.