ArticleNature medicine2014
Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 62 citations in OpenAlex.
- Trial
- A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma.Haematologica · 2019Trial
- Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.The Journal of clinical investigation · 2026Article
- Article
- Identification and validation of a thirteen-gene signature based on ubiquitin related genes in cervical cancer.Discover oncology · 2025Article
- SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Molecular functions of HAX1 during disease progress.Virus genes · 2024Review
- FBXL6 is a vulnerability in AML and unmasks proteolytic cleavage as a major experimental pitfall in myeloid cells.Leukemia · 2024Article
- The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression.Nature communications · 2024Article
- RING box protein-1(RBX1), a key component of SCF E3 ligase, induced multiple myeloma cell drug-resistance though suppressing p27.Cancer biology & therapy · 2023Article
- Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status.Cell reports. Medicine · 2023Article
- Identification of hypertrophy-modulating Cullin-RING ubiquitin ligases in primary cardiomyocytes.Frontiers in physiology · 2023Article
- The OTUD6B-LIN28B-MYC axis determines the proliferative state in multiple myeloma.The EMBO journal · 2022Article
- MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma.Blood advances · 2022Article
- Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling.Nature communications · 2022Article
- Hax-1 Regulates Radiation-Induced Mitochondrial-Dependent Apoptosis of Uveal Melanoma Cells through PI3K/AKT/eNOS Pathway.Journal of oncology · 2022Article
- The functions of long noncoding RNAs on regulation of F-box proteins in tumorigenesis and progression.Frontiers in oncology · 2022Review
- NIPA (Nuclear Interaction Partner of ALK) Is Crucial for Effective NPM-ALK Mediated Lymphomagenesis.Frontiers in oncology · 2022Article
- Ubiquitin ligases in cancer: Functions and clinical potentials.Cell chemical biology · 2021Review
- The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma.Molecular cell · 2021Article
Corrections and comments
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Authors and funding
25 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We searched for genetic alterations in human B cell lymphoma that affect the ubiquitin-proteasome system. This approach identified FBXO25 within a minimal common region of frequent deletion in mantle cell lymphoma (MCL). FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cδ (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1. Our analyses in primary human MCL identify monoallelic loss of FBXO25 and stabilizing HAX1 phosphodegron mutations. Accordingly, FBXO25 re-expression in FBXO25-deleted MCL cells promotes cell death, whereas expression of the HAX-1 phosphodegron mutant inhibits apoptosis. In addition, knockdown of FBXO25 significantly accelerated lymphoma development in Eμ-Myc mice and in a human MCL xenotransplant model. Together we identify a PRKCD-dependent proapoptotic mechanism controlling HAX-1 stability, and we propose that FBXO25 functions as a haploinsufficient tumor suppressor and that HAX1 is a proto-oncogene in MCL.
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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 Socratic graph.