Evidence map›Paper›PMID 31969556›Full record

ArticleCell death & disease2020

Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses.

Luke D Hutchinson, Nicola J Darling, Stephanos Nicolaou, Ilaria Gori, Daniel R Squair, Philip Cohen, Caroline S Hill, Gopal P Sapkota

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

Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. 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

8 authors at 3 institutions in 1 country.

Luke D HutchinsonMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, UK.
Nicola J DarlingMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, UK.
Stephanos NicolaouThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Ilaria GoriThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Daniel R SquairMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, UK.
Philip CohenMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, UK.
Caroline S HillThe Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Gopal P SapkotaMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, UK. g.sapkota@dundee.ac.uk.ORCID http://orcid.org/0000-0001-9931-3338
University of Dundee · GBThe Francis Crick Institute · GBInstitute of Cancer Research · GB

Funding

Cancer Research UK 15681Cancer Research UK FC001095Medical Research Council FC001095Medical Research Council MC_UU_00018/6Medical Research Council MC_UU_12016/3Medical Research Council MR/R021406/1Wellcome Trust FC001095
6 · The paper itself

Abstract

The signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT) and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen by using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target gene PAI-1. The screen revealed that small molecule inhibitors of salt-inducible kinases (SIKs) attenuate TGFβ-mediated transcription of PAI-1 without affecting receptor-mediated SMAD phosphorylation, SMAD complex formation or nuclear translocation. We provide evidence that genetic inactivation of SIK isoforms also attenuates TGFβ-dependent transcriptional responses. Pharmacological inhibition of SIKs by using multiple small-molecule inhibitors potentiated apoptotic cell death induced by TGFβ stimulation. Our data therefore provide evidence for a novel function of SIKs in modulating TGFβ-mediated transcriptional and cellular responses.

Indexed as

AnimalsApoptosisCell Line, TumorCell NucleusCytoplasmGene Knockout TechniquesGene SilencingHumansIndansMiceMice, Inbred C57BLPhosphorylationProtein IsoformsProtein Kinase InhibitorsProtein KinasesProtein Serine-Threonine KinasesIndansMRT199665Protein IsoformsProtein Kinase InhibitorsProtein KinasesProtein Serine-Threonine KinasesPyrimidinessalt-inducible kinase-2, humanSerpin E2Serpine2 protein, mouseSIK3 protein, humanSmad ProteinsTransforming Growth Factor beta

Identifiers

PMID31969556
PMCPMC6976658
OpenAlexW3000949338

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.