ArticleThe Journal of cell biology2010
The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation.
Article in The Journal of cell biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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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
55 citing papers in PubMed, 100 citations in OpenAlex.
- Trial
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Design of permeability-optimized target-binding macrocyclesChemical science · 2026Article
- Overcoming Ligand Discovery Challenges: Developing Peptide-Based Tracers for SPSB2.ACS chemical biology · 2026Article
- Quantitative Degradation Rate Assessment of bioPROTACs Based on Peptide Degrons, E3 Domains, Adapters and Conjugated Small Molecules.ACS chemical biology · 2026Article
- Autophagy activation by the Becn1Brain, behavior, and immunity · 2026Article
- Lysosomal quality control Review.Autophagy · 2025Review
- Article
- MDM2 induces pro-inflammatory and glycolytic responses in M1 macrophages by integrating iNOS-nitric oxide and HIF-1α pathways in mice.Nature communications · 2024Article
- Functional complementation of two splicing variants of Gustavus in Neocaridina denticulata sinensis during ovarian maturation.Scientific reports · 2024Article
- Subtle Structural Differences Affect the Inhibitory Potency of RGD-Containing Cyclic Peptide Inhibitors Targeting SPSB Proteins.International journal of molecular sciences · 2024Article
- Substantial viral diversity in bats and rodents from East Africa: insights into evolution, recombination, and cocirculation.Microbiome · 2024Article
- On the human health benefits of microalgal phytohormones: An explorativeComputational and structural biotechnology journal · 2023Article
- Dual-Role Ubiquitination Regulation Shuttling the Entire Life Cycle of the Flaviviridae.Frontiers in microbiology · 2022Review
- Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator.Communications biology · 2021Article
- Differences in gene-expression profiles in breast cancer between African and European-ancestry women.Carcinogenesis · 2020Article
- Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites.PLoS neglected tropical diseases · 2020Article
- Fbxo45 Binds SPRY Motifs in the Extracellular Domain of N-Cadherin and Regulates Neuron Migration during Brain Development.Molecular and cellular biology · 2020Article
- Macrocyclic Modalities Combining Peptide Epitopes and Natural Product Fragments.Journal of the American Chemical Society · 2020Article
- Cross-validation of existing signatures and derivation of a novel 29-gene transcriptomic signature predictive of progression to TB in a Brazilian cohort of household contacts of pulmonary TB.Tuberculosis (Edinburgh, Scotland) · 2020Observational
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inducible nitric oxide (NO) synthase (iNOS; NOS2) produces NO and related reactive nitrogen species, which are critical effectors of the innate host response and are required for the intracellular killing of pathogens such as Mycobacterium tuberculosis and Leishmania major. We have identified SPRY domain-containing SOCS (suppressor of cytokine signaling) box protein 2 (SPSB2) as a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation. SPSB2 interacts with the N-terminal region of iNOS via a binding interface on SPSB2 that has been mapped by nuclear magnetic resonance spectroscopy and mutational analyses. SPSB2-deficient macrophages showed prolonged iNOS expression, resulting in a corresponding increase in NO production and enhanced killing of L. major parasites. These results lay the foundation for the development of small molecule inhibitors that could disrupt the SPSB-iNOS interaction and thus prolong the intracellular lifetime of iNOS, which may be beneficial in chronic and persistent infections.
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What OpenQuestion holds
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.