Evidence map›Paper›PMID 25564677›Full record

ArticleScience signaling2015

The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling.

Shyam Nyati, Katrina Schinske-Sebolt, Sethuramasundaram Pitchiaya, Katerina Chekhovskiy, Areeb Chator, Nauman Chaudhry, Joseph Dosch, Marcian E Van Dort, Sooryanarayana Varambally, Chandan Kumar-Sinha and 6 more

Abstract read
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In one paragraph

Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

61 citing papers in PubMed, 94 citations in OpenAlex.

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  16. Bub1 suppresses inflammatory arthritis-associated bone loss in mice through inhibition of TNFα-mediated osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Shyam NyatiCenter for Molecular Imaging, University of Michigan, Ann Arbor, MI 48109, USA. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Katrina Schinske-SeboltDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Sethuramasundaram PitchiayaSingle Molecule Analysis in Real-Time (SMART) Center, University of Michigan, Ann Arbor, MI 48109, USA. Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Katerina ChekhovskiyDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Areeb ChatorDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Nauman ChaudhryDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Joseph DoschDepartment of Radiology, University of Michigan, Ann Arbor, MI 48109, USA.
Marcian E Van DortDepartment of Radiology, University of Michigan, Ann Arbor, MI 48109, USA.
Sooryanarayana VaramballyDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Chandan Kumar-SinhaDepartment of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Mukesh Kumar NyatiDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Dipankar RayDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Nils G WalterSingle Molecule Analysis in Real-Time (SMART) Center, University of Michigan, Ann Arbor, MI 48109, USA. Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Hongtao YuHoward Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Brian Dale RossCenter for Molecular Imaging, University of Michigan, Ann Arbor, MI 48109, USA. Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA.
Alnawaz RehemtullaCenter for Molecular Imaging, University of Michigan, Ann Arbor, MI 48109, USA. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. alnawaz@med.umich.edu.
University of Michigan–Ann Arbor · USMichigan Center for Translational Pathology · USThe University of Texas Southwestern Medical Center · US

Funding

QUANTITATION OF HUMAN BRAIN TUMOR THERAPY RESPONSE BY MRP01CA085878 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2001 to 2017
$31.9M
Small Animal Imaging CoreP50CA093990 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2002 to 2012
$19.0M
Image Biomarker Development for TreatmentEfficacy of Prostate Cancer to the BoneR01CA136892 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2009 to 2012
$2.1M
Targeting SMURF2 as a novel therapy for EGFR driven tumorsR01CA160981 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAY, DIPANKAR · 2011 to 2015
$1.4M
Howard Hughes Medical InstituteNCI NIH HHS P01 CA085878NCI NIH HHS P01CA85878NCI NIH HHS P50 CA093990NCI NIH HHS P50CA093990NCI NIH HHS P50CA093990-11NCI NIH HHS R01 CA136892NCI NIH HHS R01CA136892NCI NIH HHS R01 CA160981
6 · The paper itself

Abstract

Transforming growth factor-β (TGF-β) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-β, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF-β signaling. BUB1 interacted with TGFBRI in the presence of TGF-β and promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1 interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD-dependent transcription, and TGF-β-mediated changes in cellular phenotype including epithelial-mesenchymal transition (EMT), migration, and invasion. Knockdown of BUB1 also impaired noncanonical TGF-β signaling mediated by the kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1 to promote TGF-β signaling depended on the kinase activity of BUB1. A small-molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase-deficient mutant of BUB1 suppressed TGF-β signaling and formation of the ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase in the TGF-β pathway in a role beyond its established function in cell cycle regulation and chromosome cohesion.

Indexed as

AnimalsBlotting, WesternCell Line, TumorDimerizationFluorescent Antibody TechniqueGene Knockdown TechniquesHigh-Throughput Screening AssaysHumansImmunohistochemistryImmunoprecipitationMiceProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaRNA InterferenceRNA, Small InterferingSignal TransductionBUB1 protein, humanProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaRNA, Small InterferingSmad Proteins, Receptor-RegulatedTransforming Growth Factor beta

Identifiers

PMID25564677
PMCPMC4440544
OpenAlexW2156946175

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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.