ArticleJournal of cell science2013
Dynamic trafficking of STAT5 depends on an unconventional nuclear localization signal.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Unexpected functional role of the transactivation domain for nuclear import of STAT5.Communications biology · 2026Article
- Cellular signaling meets bacterial infection: the integrative role of STAT3.Frontiers in cellular and infection microbiology · 2026Review
- HDAC1 and HDAC2 Are Involved in Influenza A Virus-Induced Nuclear Translocation of Ectopically Expressed STAT3-GFP.Viruses · 2024Article
- LIF Promotes Sec15b-Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Multiplexed cellular profiling identifies an organoselenium compound as an inhibitor of CRM1-mediated nuclear export.Traffic (Copenhagen, Denmark) · 2022Article
- Genomic Mutations of the STAT5 Transcription Factor Are Associated with Human Cancer and Immune Diseases.International journal of molecular sciences · 2022Review
- Article
- Disruption of STAT5A and NMI signaling axis leads to ISG20-driven metastatic mammary tumors.Oncogenesis · 2021Article
- Human growth disorders associated with impaired GH action: Defects in STAT5B and JAK2.Molecular and cellular endocrinology · 2021Review
- Unphosphorylated STAT3 in heterochromatin formation and tumor suppression in lung cancer.BMC cancer · 2020Article
- Review
- Mechanisms Mediating Nuclear Trafficking Involved in Viral Propagation by DNA Viruses.Viruses · 2019Review
- Nonclassical GH Insensitivity: Characterization of Mild Abnormalities of GH Action.Endocrine reviews · 2019Review
- Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model.Cancers · 2019Article
- A novel cell-penetrating peptide protects against neuron apoptosis after cerebral ischemia by inhibiting the nuclear translocation of annexin A1.Cell death and differentiation · 2019Article
- Moderate High Temperature Condition Induces the Lactation Capacity of Mammary Epithelial Cells Through Control of STAT3 and STAT5 Signaling.Journal of mammary gland biology and neoplasia · 2018Article
- Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation.Nature communications · 2018Article
- Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness.PloS one · 2018Article
- Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate.Development (Cambridge, England) · 2016Article
- Nuclear import of the thyroid hormone receptor α1 is mediated by importin 7, importin β1, and adaptor importin α1.Molecular and cellular endocrinology · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Signal transducer and activator of transcription 5 (STAT5) is crucial for physiological processes that include hematopoiesis, liver metabolism and mammary gland development. However, aberrant continual activity of STAT5 has been causally linked to human leukemias and solid tumor formation. As a regulated transcription factor, precise cellular localization of STAT5 is essential. Conventional nuclear localization signals consist of short stretches of basic amino acids. In this study, we provide evidence that STAT5 nuclear import is dependent on an unconventional nuclear localization signal that functions within the conformation of an extensive coiled-coil domain. Both in vitro binding and in vivo functional assays reveal that STAT5 nuclear import is mediated by the importin-α3/β1 system independently of STAT5 activation by tyrosine phosphorylation. The integrity of the coiled-coil domain is essential for STAT5 transcriptional induction of the β-casein gene following prolactin stimulation as well as its ability to synergize with the glucocorticoid receptor. The glucocorticoid receptor accumulates in the nucleus in response to prolactin and this nuclear import is dependent on STAT5 nuclear import. STAT5 continually shuttles in and out of the nucleus and live cell imaging demonstrates that STAT5 nuclear export is mediated by both chromosome region maintenance 1 (Crm1)-dependent and Crm1-independent pathways. A Crm1-dependent nuclear export signal was identified within the STAT5 N-terminus. These findings provide insight into the fundamental mechanisms that regulate STAT5 nuclear trafficking and cooperation with the glucocorticoid receptor and provide a basis for clinical intervention of STAT5 function in disease.
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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.