Evidence map›Paper›PMID 21685363›Full record

ArticleGenes & development2011

A Smad action turnover switch operated by WW domain readers of a phosphoserine code.

Eric Aragón, Nina Goerner, Alexia-Ileana Zaromytidou, Qiaoran Xi, Albert Escobedo, Joan Massagué, Maria J Macias

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

146 citing papers in PubMed, 1 synthesis or guideline pooled it, 237 citations in OpenAlex.

  1. Pooled it
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  11. Molecular analysis of a self-organizing signaling pathway forProceedings of the National Academy of Sciences of the United States of America · 2024
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  14. TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024
    Review
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86 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Eric AragónStructural and Computational Biology Programme, Institute for Research in Biomedicine, Barcelona, Spain.
Nina Goerner
Alexia-Ileana Zaromytidou
Qiaoran Xi
Albert Escobedo
Joan Massagué
Maria J Macias
Institute for Research in Biomedicine · ESMemorial Sloan Kettering Cancer Center · USHoward Hughes Medical Institute · US

Funding

Transforming Growth Factor-Beta Signal TransductionR37CA034610 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI MASSAGUE, JOAN · 1995 to 2014
$6.2M
TGFB-SMAD Signaling in Stem Cell Differentiation and Tumor SuppressionR01CA034610 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MASSAGUE, JOAN · 1985 to 2019
$2.3M
NCI NIH HHS CA34610NCI NIH HHS R01 CA034610NCI NIH HHS R37 CA034610
6 · The paper itself

Abstract

When directed to the nucleus by TGF-β or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction. Here we demonstrate that there is an order of events-Smad activation first and destruction later-and that it is controlled by a switch in the recognition of Smad phosphoserines by WW domains in their binding partners. In the BMP pathway, Smad1 phosphorylation by CDK8/9 creates binding sites for the WW domains of YAP, and subsequent phosphorylation by GSK3 switches off YAP binding and adds binding sites for Smurf1 WW domains. Similarly, in the TGF-β pathway, Smad3 phosphorylation by CDK8/9 creates binding sites for Pin1 and GSK3, then adds sites to enhance Nedd4L binding. Thus, a Smad phosphoserine code and a set of WW domain code readers provide an efficient solution to the problem of coupling TGF-β signal delivery to turnover of the Smad signal transducers.

Indexed as

Gene Expression RegulationAmino Acid SequenceCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportHEK293 CellsHumansModels, MolecularMolecular Sequence DataNedd4 Ubiquitin Protein LigasesNIMA-Interacting Peptidylprolyl IsomeraseNuclear ProteinsPeptidylprolyl IsomerasePhosphorylationPhosphoserineProtein BindingProtein Structure, TertiaryCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportNedd4L protein, humanNedd4 Ubiquitin Protein LigasesNIMA-Interacting Peptidylprolyl IsomeraseNuclear ProteinsPeptidylprolyl IsomerasePhosphoserinePIN1 protein, humanSmad ProteinsSMURF1 protein, humanTranscription FactorsTransforming Growth Factor beta1Ubiquitin-Protein LigasesYY1AP1 protein, human

Identifiers

PMID21685363
PMCPMC3127429
OpenAlexW2143791437

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.