Evidence map›Paper›PMID 29127199›Full record

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.

Andrew Clerman, Zahid Noor, Rita Fishelevich, Virginia Lockatell, Brian S Hampton, Nirav G Shah, Mariah V Salcedo, Nevins W Todd, Sergei P Atamas, Irina G Luzina

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Innovation through imitation: IL-33 decoys show promise in pulmonary fibrosis.The Journal of pharmacology and experimental therapeutics · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. 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 · 2022
    Article
  10. The Paradigm Change of IL-33 in Vascular Biology.International journal of molecular sciences · 2021
    Review
  11. Article
  12. Article
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

10 authors at 2 institutions in 1 country.

Andrew ClermanFrom the Department of Medicine and.
Zahid NoorFrom the Department of Medicine and.
Rita FishelevichFrom the Department of Medicine and.
Virginia LockatellFrom the Department of Medicine and.
Brian S Hamptonthe Center for Vascular and Inflammatory Diseases & Center for Innovative Biomedical Resources, University of Maryland School of Medicine, Baltimore, Maryland 21201 and.
Nirav G ShahFrom the Department of Medicine and.
Mariah V SalcedoFrom the Department of Medicine and.
Nevins W ToddFrom the Department of Medicine and.
Sergei P AtamasFrom the Department of Medicine and satamas@umaryland.edu.
Irina G LuzinaFrom the Department of Medicine and.
Veterans Health Administration · USUniversity of Maryland, Baltimore · US

Funding

The Mechanisms of Profibrotic Sensitization by IL33R01HL126897 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI LUZINA, IRINA G. · 2015 to 2018
$1.4M
The Central Role of IL-33 in Immune-Mediated ScarringI01BX002499 · VA · BALTIMORE VA MEDICAL CENTER · PI LUZINA, IRINA G. · 2015 to 2020
–
Integrin-dependent mechanism of T cell-mediated pulmonary fibrosisI01CX000101 · VA · BALTIMORE VA MEDICAL CENTER · PI LUZINA, IRINA G. · 2009 to 2017
–
BLRD VA I01 BX002499CSRD VA I01 CX000101NHLBI NIH HHS R01 HL126897
6 · The paper itself

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.

Indexed as

Amino Acid Sequencebeta KaryopherinsCell NucleusCytoplasmHEK293 CellsHeLa CellsHumansInterleukin-33Nuclear Localization SignalsNuclear ProteinsProtein BindingProtein Interaction Domains and MotifsProtein TransportProteolysisbeta KaryopherinsIL33 protein, humanInterleukin-33IPO5 protein, humanNuclear Localization SignalsNuclear Proteinsfibroblastinterleukin-33nuclear translocationproteasomeprotein degradationprotein-protein interaction

Identifiers

PMID29127199
PMCPMC5766934
OpenAlexW2767919706

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.