ArticleThe Journal of clinical investigation2024
Parkin activates innate immunity and promotes antitumor immune responses.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
What it found
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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.
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
12 citing papers in PubMed.
- Decoding Mitophagy in Breast Cancer: Biological Mechanisms, Dual Roles, and Clinical Implications.Cells · 2026Review
- TRAIP Mediates Alcohol-Induced Liver Injury through Regulating β-catenin Ubiquitin Degradation via Direct Interaction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Formation of tertiary lymphoid structures drives Parkin antitumor immunity.Science advances · 2026Article
- Correlation of AHR Activation-Induced Suppression of PWM-Stimulated IgG and IgG-Triggered Signaling in Human PBMCs.Antibodies (Basel, Switzerland) · 2026Article
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- E3 Ligases and Deubiquitinases in Controlling High-Mobility Group Box (HMGB) Protein Functions.International journal of molecular sciences · 2026Review
- Tissue-specific transcriptional epistasis between Prkn and Lrrk2 during mycobacterial infection.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Parkin Induces Ubiquitination and Large Extracellular Vesicle Release of HMGB1 to Activate Antitumor Immunity.Cancer research · 2025Article
- Interferon signaling pathways in health and disease.Molecular biomedicine · 2025Review
- Parkin modulates the hepatocellular carcinoma microenvironment by regulating PD-1/PD-L1 signalling.Journal of advanced research · 2025Article
- Parkin paves the path to antitumor immunity: Expanding Parkin's role as a tumor suppressor.The Journal of clinical investigation · 2024Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
The activation of innate immunity and associated interferon (IFN) signaling have been implicated in cancer, but the regulators are elusive and links to tumor suppression remain undetermined. Here, we found that Parkin, an E3 ubiquitin ligase altered in Parkinson's Disease, was epigenetically silenced in cancer and its reexpression by clinically approved demethylating therapy stimulated transcription of a potent IFN response in tumor cells. This pathway required Parkin E3 ubiquitin ligase activity, involved the subcellular trafficking and release of the alarmin High Mobility Group Box 1 (HMGB1) and was associated with inhibition of NF-κB gene expression. In turn, Parkin-expressing cells released an IFN secretome that upregulated effector and cytotoxic CD8+ T cell markers, lowered the expression of immune inhibitory receptors TIM3 and LAG3, and stimulated high content of the self renewal/stem cell factor, TCF1. PRKN-induced CD8+ T cells selectively accumulated in the microenvironment and inhibited transgenic and syngeneic tumor growth in vivo. Therefore, Parkin is an epigenetically regulated activator of innate immunity and dual mode tumor suppressor, inhibiting intrinsic tumor traits of metabolism and cell invasion, while simultaneously reinvigorating CD8 T cell functions in the microenvironment.
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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.