ArticleThe Journal of biological chemistry2017
The full-length interleukin-33 (FLIL33)-importin-5 interaction does not regulate nuclear localization of FLIL33 but controls its intracellular degradation.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- SHARPIN restrains IL-33 release by stromal cells to control ILC2 inflammation.Science advances · 2026Article
- The nuclear transport factor IPO5 revealed as a critical mediator of male germline development†.Biology of reproduction · 2025Article
- Innovation through imitation: IL-33 decoys show promise in pulmonary fibrosis.The Journal of pharmacology and experimental therapeutics · 2025Article
- Therapeutic targeting of full-length interleukin-33 protein levels with cell-permeable decoy peptides attenuates fibrosis in the bleomycin model in vivo.The Journal of pharmacology and experimental therapeutics · 2025Article
- Unpacking the complexity of nuclear IL-33 (nIL-33): a crucial regulator of transcription and signal transduction.Journal of cell communication and signaling · 2023Review
- The IL-33:ST2 axis is unlikely to play a central fibrogenic role in idiopathic pulmonary fibrosis.Respiratory research · 2023Article
- Full-length IL-33 augments pulmonary fibrosis in an ST2- and Th2-independent, non-transcriptomic fashion.Cellular immunology · 2023Article
- Porcine Circovirus Type 2 Hijacks Host IPO5 to Sustain the Intracytoplasmic Stability of Its Capsid Protein.Journal of virology · 2022Article
- Ischemia reperfusion injury facilitates lung allograft acceptance through IL-33-mediated activation of donor-derived IL-5 producing group 2 innate lymphoid cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- The Paradigm Change of IL-33 in Vascular Biology.International journal of molecular sciences · 2021Review
- Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner.Cellular immunology · 2020Article
- Identification of the IL-33 protein segment that controls subcellular localization, extracellular secretion, and functional maturation.Cytokine · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Human mature IL-33 is a member of the IL-1 family and a potent regulator of immunity through its pro-T helper cell 2 activity. Its precursor form, full-length interleukin-33 (FLIL33), is an intranuclear protein in many cell types, including fibroblasts, and its intracellular levels can change in response to stimuli. However, the mechanisms controlling the nuclear localization of FLIL33 or its stability in cells are not understood. Here, we identified importin-5 (IPO5), a member of the importin family of nuclear transport proteins, as an intracellular binding partner of FLIL33. By overexpressing various FLIL33 protein segments and variants in primary human lung fibroblasts and HEK293T cells, we show that FLIL33, but not mature interleukin-33, physically interacts with IPO5 and that this interaction localizes to a cluster of charged amino acids (positions 46-56) but not to an adjacent segment (positions 61-67) in the FLIL33 N-terminal region. siRNA-mediated IPO5 knockdown in cell culture did not affect nuclear localization of FLIL33. However, the IPO5 knockdown significantly decreased the intracellular levels of overexpressed FLIL33, reversed by treatment with the 20S proteasome inhibitor bortezomib. Furthermore, FLIL33 variants deficient in IPO5 binding remained intranuclear and exhibited decreased levels, which were also restored by the bortezomib treatment. These results indicate that the interaction between FLIL33 and IPO5 is localized to a specific segment of the FLIL33 protein, is not required for nuclear localization of FLIL33, and protects FLIL33 from proteasome-dependent degradation.
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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.