ArticleeLife2022
Arl15 upregulates the TGFβ family signaling by promoting the assembly of the Smad-complex.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- A meta-analysis of genome-wide association studies revealed significant QTL and candidate genes for loin muscle area in three breeding pigs.Scientific reports · 2025Pooled it
- Reimagining VEGF Therapy: The Role of PLCγ2 in Pan-Organ Endothelial Networks.Advances in wound care · 2026Article
- Systematic identification of Oct4 transcriptional targets in embryonic stem cells using the auxin-inducible degron system and nascent RNA sequencing.Cell regeneration (London, England) · 2025Article
- The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease.International journal of molecular sciences · 2025Review
- TRPM7 channel activity promotes the pathogenesis of abdominal aortic aneurysms.Nature cardiovascular research · 2025Article
- Role of transforming growth factor-β in peripheral nerve regeneration.Neural regeneration research · 2024Review
- Open MoA: revealing the mechanism of action (MoA) based on network topology and hierarchy.Bioinformatics (Oxford, England) · 2023Article
- Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.eLife · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hallmark event of the canonical transforming growth factor β (TGFβ) family signaling is the assembly of the Smad-complex, consisting of the common Smad, Smad4, and phosphorylated receptor-regulated Smads. How the Smad-complex is assembled and regulated is still unclear. Here, we report that active Arl15, an Arf-like small G protein, specifically binds to the MH2 domain of Smad4 and colocalizes with Smad4 at the endolysosome. The binding relieves the autoinhibition of Smad4, which is imposed by the intramolecular interaction between its MH1 and MH2 domains. Activated Smad4 subsequently interacts with phosphorylated receptor-regulated Smads, forming the Smad-complex. Our observations suggest that Smad4 functions as an effector and a GTPase activating protein (GAP) of Arl15. Assembly of the Smad-complex enhances the GAP activity of Smad4 toward Arl15, therefore dissociating Arl15 before the nuclear translocation of the Smad-complex. Our data further demonstrate that Arl15 positively regulates the TGFβ family signaling.
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Registered trials
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.