ArticleLeukemia2022
Small molecule inhibition of deubiquitinating enzyme JOSD1 as a novel targeted therapy for leukemias with mutant JAK2.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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.
Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Targeting DESI2 as a Novel Therapeutic Strategy for JAK2-Mutant Leukemias.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Early peripheral blood gene expression predicts 90-day outcomes following subarachnoid hemorrhage.Journal of neuroinflammation · 2025Article
- High-Throughput Synthesis and Screening of a Cyanimide Library Identifies Selective Inhibitors of ISG15-Specific Protease mUSP18.Angewandte Chemie (International ed. in English) · 2025Article
- Josephin Domain Containing 2 (JOSD2) inhibition as Pan-KRAS-mutation-targeting strategy for colorectal cancer.Nature communications · 2025Article
- Rapid Detection ofBiomolecules · 2024Article
- Deubiquitinase JOSD1 tempers hepatic proteotoxicity.Cell death discovery · 2024Article
- Regulation of Hippo/YAP axis in colon cancer progression by the deubiquitinase JOSD1.Cell death discovery · 2024Article
- Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1.Nature communications · 2024Article
- DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases.Biomolecules · 2023Review
- Review
- MALDI-TOF Mass Spectrometry for interrogating ubiquitin enzymes.Frontiers in molecular biosciences · 2023Article
- Structural basis for specific inhibition of the deubiquitinase UCHL1.Nature communications · 2022Article
- Inhibition of the deubiquitinating enzyme USP47 as a novel targeted therapy for hematologic malignancies expressing mutant EZH2.Leukemia · 2022Article
- Development and validation of a transcriptomic signature-based model as the predictive, preventive, and personalized medical strategy for preterm birth within 7 days in threatened preterm labor women.The EPMA journal · 2022Article
- MJDs family members: Potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma.Frontiers in genetics · 2022Article
- Deubiquitinase JOSD1 promotes tumor progression via stabilizing Snail in lung adenocarcinoma.American journal of cancer research · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the Janus Kinase 2 (JAK2) gene resulting in constitutive kinase activation represent the most common genetic event in myeloproliferative neoplasms (MPN), a group of diseases involving overproduction of one or more kinds of blood cells, including red cells, white cells, and platelets. JAK2 kinase inhibitors, such as ruxolitinib, provide clinical benefit, but inhibition of wild-type (wt) JAK2 limits their clinical utility due to toxicity to normal cells, and small molecule inhibition of mutated JAK2 kinase activity can lead to drug resistance. Here, we present a strategy to target mutated JAK2 for degradation, using the cell's intracellular degradation machinery, while sparing non-mutated JAK2. We employed a chemical genetics screen, followed by extensive selectivity profiling and genetic studies, to identify the deubiquitinase (DUB), JOSD1, as a novel regulator of mutant JAK2. JOSD1 interacts with and stabilizes JAK2-V617F, and inactivation of the DUB leads to JAK2-V617F protein degradation by increasing its ubiquitination levels, thereby shortening its protein half-life. Moreover, targeting of JOSD1 leads to the death of JAK2-V617F-positive primary acute myeloid leukemia (AML) cells. These studies provide a novel therapeutic approach to achieving selective targeting of mutated JAK2 signaling in MPN.
Indexed as
Identifiers
What Socratic 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 Socratic graph.