Evidence map›Paper›PMID 23840619›Full record

ArticlePloS one2013

Identification of a Novel Link between the Protein Kinase NDR1 and TGFβ Signaling in Epithelial Cells.

Isabelle Pot, Shachi Patel, Lili Deng, Amrita Singh Chandhoke, Chi Zhang, Azad Bonni, Shirin Bonni

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. The STK38-XPO1 axis, a new actor in physiology and cancer.Cellular and molecular life sciences : CMLS · 2021
    Review
  6. Article
  7. Article
  8. Article
  9. The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  10. Article
  11. Article
  12. The ubiquitin ligase Cullin5Scientific reports · 2017
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
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 2 institutions in 2 countries.

Isabelle PotSouthern Alberta Cancer Research Institute and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
Shachi Patel
Lili Deng
Amrita Singh Chandhoke
Chi Zhang
Azad Bonni
Shirin Bonni
University of Calgary · CAHarvard University · US

Funding

SIGNAL TRANSDUCTION PATHWAYS REGULATING NEURON SURVIVALR01NS041021 · NINDS · WASHINGTON UNIVERSITY · PI GABEL, HARRISON W · 2001 to 2023
$7.7M
CIHRNINDS NIH HHS R01 NS041021
6 · The paper itself

Abstract

Transforming growth factor-beta (TGFβ) is a secreted polypeptide that plays essential roles in cellular development and homeostasis. Although mechanisms of TGFβ-induced responses have been characterized, our understanding of TGFβ signaling remains incomplete. Here, we uncover a novel function for the protein kinase NDR1 (nuclear Dbf2-related 1) in TGFβ responses. Using an immunopurification approach, we find that NDR1 associates with SnoN, a key component of TGFβ signaling. Knockdown of NDR1 by RNA interference promotes the ability of TGFβ to induce transcription and cell cycle arrest in NMuMG mammary epithelial cells. Conversely, expression of NDR1 represses TGFβ-induced transcription and inhibits the ability of TGFβ to induce cell cycle arrest in NMuMG cells. Mechanistically, we find that NDR1 acts in a kinase-dependent manner to suppress the ability of TGFβ to induce the phosphorylation and consequent nuclear accumulation of Smad2, which is critical for TGFβ-induced transcription and responses. Strikingly, we also find that TGFβ reciprocally regulates NDR1, whereby TGFβ triggers the degradation of NDR1 protein. Collectively, our findings define a novel and intimate link between the protein kinase NDR1 and TGFβ signaling. NDR1 suppresses TGFβ-induced transcription and cell cycle arrest, and counteracting NDR1's negative regulation, TGFβ signaling induces the downregulation of NDR1 protein. These findings advance our understanding of TGFβ signaling, with important implications in development and tumorigenesis.

Indexed as

Signal TransductionAnimalsCell Cycle CheckpointsCell Cycle ProteinsCell LineCell ProliferationEpithelial CellsGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsMiceN-myc Downstream-Regulated Gene 1 ProteinPhosphorylationProtein Serine-Threonine KinasesProteolysisProto-Oncogene ProteinsCell Cycle ProteinsIntracellular Signaling Peptides and ProteinsN-myc Downstream-Regulated Gene 1 ProteinProtein Serine-Threonine KinasesProto-Oncogene ProteinsSKIL protein, humanSmad2 ProteinSTK38 protein, humanTransforming Growth Factor beta

Identifiers

PMID23840619
PMCPMC3694053
OpenAlexW2160517146

What OpenQuestion holds

Textmetadata
LicenceCC0
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.