ArticleMolecular and cellular biology2006
The mechanism of nuclear export of Smad3 involves exportin 4 and Ran.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 98 citations in OpenAlex.
- Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study.Radiation oncology (London, England) · 2011Trial
- N-Terminal Basic Helix and S120 Phosphorylation Cooperatively Regulate Nuclear Localization of UBE2A/B in Mechanotransduction.Biology · 2026Article
- The long noncoding RNA VIM-AS1 and nucleoporin Nup358/RanBP2 regulate SMAD nuclear accumulation during TGF-β signaling.Nucleic acids research · 2026Article
- TGF-beta inhibitors in cancer therapy: a review of the TGF-beta signal transduction pathway and current developments.EXCLI journal · 2026Review
- Viral interference of nucleocytoplasmic transport.The Journal of biological chemistry · 2025Review
- Proteomic signature of aging in bloodstain samples: a preliminary study.BMC genomics · 2025Article
- A positive feedback loop between SMAD3 and PINK1 in regulation of mitophagy.Cell discovery · 2025Article
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Comprehensive bioinformatics analysis on exportins in lung adenocarcinoma and lung squamous cell carcinoma.Journal of thoracic disease · 2023Article
- Rhinovirus protease cleavage of nucleoporins: perspective on implications for airway remodeling.Frontiers in microbiology · 2023Article
- Exportin 4 depletion leads to nuclear accumulation of a subset of circular RNAs.Nature communications · 2022Article
- Karyopherin-mediated nucleocytoplasmic transport.Nature reviews. Molecular cell biology · 2022Review
- Karyopherin abnormalities in neurodegenerative proteinopathies.Brain : a journal of neurology · 2021Review
- Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration.International journal of molecular sciences · 2021Review
- TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Subcellular Localization of Epstein-Barr Virus BLLF2 and Its Underlying Mechanisms.Frontiers in microbiology · 2021Article
- Identification of novel splice mutation in SMAD3 in two Cypriot families with nonsyndromic thoracic aortic aneurysm. Two case reports.Molecular genetics & genomic medicine · 2020Article
- TGF-β Signaling.Biomolecules · 2020Review
- Review
- Liver Cancer Gene Discovery Using Gene Targeting, Sleeping Beauty, and CRISPR/Cas9.Seminars in liver disease · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor beta (TGF-beta) receptors phosphorylate Smad3 and induce its nuclear import so it can regulate gene transcription. Smad3 can return to the cytoplasm to propagate further cycles of signal transduction or to be degraded. We demonstrate that Smad3 is exported by a constitutive mechanism that is insensitive to leptomycin B. The Mad homology 2 (MH2) domain is responsible for Smad3 export, which requires the GTPase Ran. Inactive, GDP-locked RanT24N or nuclear microinjection of Ran GTPase activating protein 1 blocked Smad3 export. Inactivation of the Ran guanine nucleotide exchange factor RCC1 inhibited Smad3 export and led to nuclear accumulation of phosphorylated Smad3. A screen for importin/exportin family members that associate with Smad3 identified exportin 4, which binds a conserved peptide sequence in the MH2 domain of Smad3 in a Ran-dependent manner. Exportin 4 is sufficient for carrying the in vitro nuclear export of Smad3 in cooperation with Ran. Knockdown of endogenous exportin 4 completely abrogates the export of endogenous Smad3. A short peptide representing the minimal interaction domain in Smad3 effectively competes with Smad3 association to exportin 4 and blocks nuclear export of Smad3 in vivo. We thus delineate a novel nuclear export pathway for Smad3.
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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.