Evidence map›Paper›PMID 31782549›Full record

ArticleThe EMBO journal2020

Elucidation of WW domain ligand binding specificities in the Hippo pathway reveals STXBP4 as YAP inhibitor.

Rebecca E Vargas, Vy Thuy Duong, Han Han, Albert Paul Ta, Yuxuan Chen, Shiji Zhao, Bing Yang, Gayoung Seo, Kimberly Chuc, Sunwoo Oh and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

22 citing papers in PubMed, 36 citations in OpenAlex.

  1. Comparing YAPBiomolecules · 2026
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  3. Proteome-wide prediction of interactions between structured domains and peptide motifs reveals functionally coherent subnetworks.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

16 authors at 3 institutions in 2 countries.

Rebecca E VargasDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Vy Thuy DuongDepartment of Chemistry, University of California, Irvine, Irvine, CA, USA.
Han HanDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Albert Paul TaDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Yuxuan ChenDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Shiji ZhaoDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Bing YangDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Gayoung SeoDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Kimberly ChucDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Sunwoo OhDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Amal El AliDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
Olga V RazorenovaDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
Junjie ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-1493-2189
Ray LuoDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0002-6346-8271
Xu LiSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.ORCID 0000-0002-9401-6382
Wenqi WangDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0003-4053-5088
University of California, Irvine · USThe University of Texas MD Anderson Cancer Center · USWestlake University · CN

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
MINORITY BIOMEDICAL RESEARCHERS PROGRAMR25GM055246 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI MOTA-BRAVO, LUIS M · 1996 to 2022
$15.3M
AMBER force field consortium: a coherent biomolecular simulation platformR01GM079383 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CIEPLAK, PIOTR, DUAN, YONG · 2007 to 2017
$4.7M
Multiscale Models of Wound Cell Plasticity for RegenerationU01AR073159 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAI, XING, NIE, QING · 2018 to 2022
$3.5M
Multi-scaled Modeling of Electrostatic and Polarization Effects in BiomoleculesR35GM130367 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI RAY LUO · 2019 to 2026
$3.0M
Regulation and function of the Hippo pathway in growth controlR01GM126048 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Wenqi Wang · 2018 to 2026
$3.0M
Mathematical, Computational and Systems BiologyT32EB009418 · NIBIB · UNIVERSITY OF CALIFORNIA-IRVINE · PI LANDER, ARTHUR D, NIE, QING · 2009 to 2019
$2.4M
American Cancer Society (ACS) RSG-18-009-01-CCGNCI NIH HHS P30 CA062203NIAMS NIH HHS U01 AR073159NIBIB NIH HHS T32 EB009418NIGMS NIH HHS R01 GM079383NIGMS NIH HHS R01 GM126048NIGMS NIH HHS R25 GM055246NIGMS NIH HHS R35 GM130367U.S. Department of Defense (DOD) W81XWH-09-1-0409
6 · The paper itself

Abstract

The Hippo pathway, which plays a critical role in organ size control and cancer, features numerous WW domain-based protein-protein interactions. However, ~100 WW domains and 2,000 PY motif-containing peptide ligands are found in the human proteome, raising a "WW-PY" binding specificity issue in the Hippo pathway. In this study, we have established the WW domain binding specificity for Hippo pathway components and uncovered a unique amino acid sequence required for it. By using this criterion, we have identified a WW domain-containing protein, STXBP4, as a negative regulator of YAP. Mechanistically, STXBP4 assembles a protein complex comprising α-catenin and a group of Hippo PY motif-containing components/regulators to inhibit YAP, a process that is regulated by actin cytoskeleton tension. Interestingly, STXBP4 is a potential tumor suppressor for human kidney cancer, whose downregulation is correlated with YAP activation in clear cell renal cell carcinoma. Taken together, our study not only elucidates the WW domain binding specificity for the Hippo pathway, but also reveals STXBP4 as a player in actin cytoskeleton tension-mediated Hippo pathway regulation.

Indexed as

Gene Expression Regulation, NeoplasticSignal TransductionAdaptor Proteins, Signal TransducingAnimalsApoptosisBiomarkers, TumorCarcinoma, Renal CellCell ProliferationFemaleHippo Signaling PathwayHumansKidney NeoplasmsMiceMice, Inbred BALB CMice, NudePrognosisAdaptor Proteins, Signal TransducingBiomarkers, TumorProtein Serine-Threonine KinasesSTXBP4 protein, humanTranscription FactorsVesicular Transport ProteinsYAP1 protein, humanYAP-Signaling ProteinsPY motifSTXBP4the Hippo pathwayWW domainYAP

Identifiers

PMID31782549
PMCPMC6939200
OpenAlexW2990219485

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.