ArticleBlood2014
MLN4924, an NAE inhibitor, suppresses AKT and mTOR signaling via upregulation of REDD1 in human myeloma cells.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 78 citations in OpenAlex.
- Article
- Inhibition of FOXM1 Synergizes with BH3 Mimetics Venetoclax and Sonrotoclax in Killing Multiple Myeloma Cells through Repressing MYC Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- The Cullin3-Rbx1-KLHL9 E3 ubiquitin ligase complex ubiquitinates Rheb and supports amino acid-induced mTORC1 activation.Cell reports · 2025Article
- YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway.Biology direct · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Pharmacologic targeting of Nedd8-activating enzyme reinvigorates T-cell responses in lymphoid neoplasia.Leukemia · 2023Article
- NEDD8-Activating Enzyme Inhibitor MLN4924 Inhibits Both the Tumor Stroma and Angiogenesis in Pancreatic Cancer via Gli1 and REDD1.Digestive diseases and sciences · 2023Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- REDD1 gene knockout alleviates vascular smooth muscle cell remodeling in pulmonary hypertension.American journal of translational research · 2022Article
- Gene expression profiling reveals the genomic changes caused by MLN4924 and the sensitizing effects of NAPEPLD knockdown in pancreatic cancer.Cell cycle (Georgetown, Tex.) · 2022Article
- Synthetic Lethality Screening Highlights Colorectal Cancer Vulnerability to Concomitant Blockade of NEDD8 and EGFR Pathways.Cancers · 2021Article
- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
- Neddylation of PTEN regulates its nuclear import and promotes tumor development.Cell research · 2021Article
- Perspectives on the Clinical Development of NRF2-Targeting Drugs.Handbook of experimental pharmacology · 2021Review
- Inhibition of HDAC6 Activity Protects Against Endothelial Dysfunction and AtherogenesisFrontiers in physiology · 2021Article
- Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy.Cancers · 2020Review
- Downregulation of PA28α induces proteasome remodeling and results in resistance to proteasome inhibitors in multiple myeloma.Blood cancer journal · 2020Article
- Impact of HDAC Inhibitors on Protein Quality Control Systems: Consequences for Precision Medicine in Malignant Disease.Frontiers in cell and developmental biology · 2020Review
- Targeting Cullin-RING E3 Ligases for Radiosensitization: From NEDDylation Inhibition to PROTACs.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The function and survival of normal and malignant plasma cells depends on the elaborately regulated ubiquitin proteasome system. Proteasome inhibitors such as bortezomib have proved to be highly effective in the treatment of multiple myeloma (MM), and their effects are related to normal protein homeostasis which is critical for plasma cell survival. Many ubiquitin ligases are regulated by conjugation with NEDD8. Therefore, neddylation may also impact survival and proliferation of malignant plasma cells. Here, we show that MLN4924, a potent NEDD8 activating enzyme (NAE) inhibitor, induced cytotoxicity in MM cell lines, and its antitumor effect is associated with suppression of the AKT and mammalian target of rapamycin (mTOR) signaling pathways through increased expression of REDD1. Combining MLN4924 with the proteasome inhibitor bortezomib induces synergistic apoptosis in MM cell lines which can overcome the prosurvival effects of growth factors such as interleukin-6 and insulin-like growth factor-1. Altogether, our findings demonstrate an important function for REDD1 in MLN4924-induced cytotoxicity in MM and also provide a promising therapeutic combination strategy for myeloma.
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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.