Evidence map›Paper›PMID 25561725›Full record

ArticleThe Journal of biological chemistry2015

Structure of neuroblastoma suppressor of tumorigenicity 1 (NBL1): insights for the functional variability across bone morphogenetic protein (BMP) antagonists.

Kristof Nolan, Chandramohan Kattamuri, David M Luedeke, Elizabeth B Angerman, Scott A Rankin, Mariana L Stevens, Aaron M Zorn, Thomas B Thompson

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Structural Biology and Evolution of the TGF-β Family.Cold Spring Harbor perspectives in biology · 2016
    Review
  19. Article
  20. Article
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

8 authors at 1 institution in 1 country.

Kristof NolanDepartment of Molecular Genetics, Biochemistry, and Microbiology, The University of Cincinnati, Cincinnati, Ohio 45267 and.
Chandramohan KattamuriDepartment of Molecular Genetics, Biochemistry, and Microbiology, The University of Cincinnati, Cincinnati, Ohio 45267 and.
David M LuedekeDepartment of Molecular Genetics, Biochemistry, and Microbiology, The University of Cincinnati, Cincinnati, Ohio 45267 and.
Elizabeth B AngermanDepartment of Molecular Genetics, Biochemistry, and Microbiology, The University of Cincinnati, Cincinnati, Ohio 45267 and.
Scott A RankinPerinatal Institute, Cincinnati Children's Research Foundation and Department of Pediatrics, The University of Cincinnati, Cincinnati, Ohio 45229.
Mariana L StevensPerinatal Institute, Cincinnati Children's Research Foundation and Department of Pediatrics, The University of Cincinnati, Cincinnati, Ohio 45229.
Aaron M ZornPerinatal Institute, Cincinnati Children's Research Foundation and Department of Pediatrics, The University of Cincinnati, Cincinnati, Ohio 45229.
Thomas B ThompsonDepartment of Molecular Genetics, Biochemistry, and Microbiology, The University of Cincinnati, Cincinnati, Ohio 45267 and. Electronic address: tom.thompson@uc.edu.
University of Cincinnati · US

Funding

Training Program in Cancer TherapeuticsT32CA117846 · NCI · UNIVERSITY OF CINCINNATI · PI PRICE, CAROLYN M, TAKIAR, VINITA · 2006 to 2022
$6.5M
Molecular Basis of Liver Development.R01DK070858 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI ZORN, AARON M · 2007 to 2017
$2.9M
Structure-Function Investigation of DAN-mediated BMP AntagonismR01GM114640 · NIGMS · UNIVERSITY OF CINCINNATI · PI THOMPSON, THOMAS B · 2015 to 2018
$1.7M
Structural basis of antagonism within the TGFbeta-superfamilyR01GM084186 · NIGMS · UNIVERSITY OF CINCINNATI · PI THOMPSON, THOMAS B · 2008 to 2012
$1.6M
NCI NIH HHS T32 CA117846NIDDK NIH HHS R01 DK070858NIGMS NIH HHS R01 GM084186NIGMS NIH HHS R01 GM114640
6 · The paper itself

Abstract

Bone morphogenetic proteins (BMPs) are antagonized through the action of numerous extracellular protein antagonists, including members from the differential screening-selected gene aberrative in neuroblastoma (DAN) family. In vivo, misregulation of the balance between BMP signaling and DAN inhibition can lead to numerous disease states, including cancer, kidney nephropathy, and pulmonary arterial hypertension. Despite this importance, very little information is available describing how DAN family proteins effectively inhibit BMP ligands. Furthermore, our understanding for how differences in individual DAN family members arise, including affinity and specificity, remains underdeveloped. Here, we present the structure of the founding member of the DAN family, neuroblastoma suppressor of tumorigenicity 1 (NBL1). Comparing NBL1 to the structure of protein related to Dan and Cerberus (PRDC), a more potent BMP antagonist within the DAN family, a number of differences were identified. Through a mutagenesis-based approach, we were able to correlate the BMP binding epitope in NBL1 with that in PRDC, where introduction of specific PRDC amino acids in NBL1 (A58F and S67Y) correlated with a gain-of-function inhibition toward BMP2 and BMP7, but not GDF5. Although NBL1(S67Y) was able to antagonize BMP7 as effectively as PRDC, NBL1(S67Y) was still 32-fold weaker than PRDC against BMP2. Taken together, this data suggests that alterations in the BMP binding epitope can partially account for differences in the potency of BMP inhibition within the DAN family.

Indexed as

Mutation, MissenseAmino Acid SubstitutionAnimalsBone Morphogenetic Protein 2Bone Morphogenetic Protein 7Cell Cycle ProteinsCHO CellsCricetinaeCricetulusCytokinesHumansIntercellular Signaling Peptides and ProteinsMutagenesisProteinsProtein Structure, TertiaryStructure-Activity RelationshipBMP2 protein, humanBMP7 protein, humanBone Morphogenetic Protein 2Bone Morphogenetic Protein 7Cell Cycle ProteinsCytokinesGREM2 protein, humanIntercellular Signaling Peptides and ProteinsNBL1 protein, humanProteinsBone Morphogenetic Protein (BMP)Differential Screening-aberrative in Neuroblastoma (DAN)Extracellular AntagonismMutagenesisNeuroblastoma Suppressor of Tumorigenicity 1 (NBL1)Protein Related to Dan and Cerberus (PRDC)SOSTStructural BiologyTransforming Growth Factor β(TGF-B)X-ray Crystallography

Identifiers

PMID25561725
PMCPMC4335214
OpenAlexW2083333330

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.