ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Role of cereblon in angiogenesis and in mediating the antiangiogenic activity of immunomodulatory drugs.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Review
- Cereblon (CRBN) inhibits prostate cancer metastasis by negatively regulating 6-phosphogluconate dehydrogenase (6PGD).Oncogene · 2026Article
- Monoterpenoid fluorophthalimide IMiDs that lack human cereblon binding: synthesis and anti-proliferative, anti-angiogenic and anti-inflammatory activities.Biochemical and biophysical research communications · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Revisiting the antiangiogenic mechanisms of fluorinated thalidomide derivatives.Bioorganic & medicinal chemistry letters · 2024Article
- Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma.Biomolecules · 2024Article
- Benzothiazole-Phthalimide Hybrids as Anti-Breast Cancer and Antimicrobial Agents.Antibiotics (Basel, Switzerland) · 2023Article
- Thalidomide upper limb embryopathy - pathogenesis, past and present management and future considerations.The Journal of hand surgery, European volume · 2023Review
- A New Generation of IMiDs as Treatments for Neuroinflammatory and Neurodegenerative Disorders.Biomolecules · 2023Review
- Molecular and Structural Characterization of Lenalidomide-Mediated Sequestration of eIF3i.ACS chemical biology · 2022Article
- From the Farm to the Lab: How Chicken Embryos Contribute to the Field of Teratology.Frontiers in genetics · 2021Review
- Comparative Genomics Identifies Putative Interspecies Mechanisms Underlying Crbn-Sall4-Linked Thalidomide Embryopathy.Frontiers in genetics · 2021Article
- On the correlation of cereblon binding, fluorination and antiangiogenic properties of immunomodulatory drugs.Biochemical and biophysical research communications · 2021Article
- Antiangiogenic Activity and in Silico Cereblon Binding Analysis of Novel Thalidomide Analogs.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cereblon (CRBN) is a substrate recruiter element of the E3 cullin 4-RING ubiquitin ligase complex, and a binding target of immunomodulatory agents (IMiDs). CRBN is responsible for the pleiotropic effects of IMiDs, yet its function in angiogenesis and in mediating the antiangiogenic effects of IMiDs remains unclear. We investigated the role of CRBN in the angiogenic process and in propagating the antiangiogenic effects of IMiDs in vitro. siRNA-mediated CRBN knock down in human endothelial cells (HUVEC and HMVEC-L), did not affect endothelial cell proliferation, migration, or tube formation. Using CRBN-deficient mice, we further demonstrated that microvessal formation can occur independently of cereblon in the ex vivo mouse aortic ring model. The cereblon E3 ubiquitin ligase complex can recruit endothelial cell-specific factors, AGO2 (associated with angiogenesis), and SALL4 (associated with embryogenesis/angiogenesis), for ubiquitin-mediated degradation. Knockdown of CRBN caused a corresponding increase in AGO2 and SALL4 protein expression and IMiD treatment was able to rescue the siCRBN effect to increase the CRBN expression. These findings suggest one potential mechanism of action that likely involves a tightly coordinated regulation of CRBN with endothelial cell targets and highlight the need to further elucidate the mechanism(s), which could include cereblon-independent pathways, through which IMiDs exert their antiangiogenic effects.
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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.