ArticleCell stem cell2022
TRAF6 functions as a tumor suppressor in myeloid malignancies by directly targeting MYC oncogenic activity.
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Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39citing papers in PubMed
8.8field-weighted citation impact, top 1% of its field
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39 citing papers in PubMed, 58 citations in OpenAlex.
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- The structure and functions of TRAF families and recent advances of TRAFs in leukemia.Frontiers in oncology · 2026Review
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- Nonproteolytic ubiquitination regulates chromatin occupancy by the NCoR/SMRT/HDAC3 corepressor complex in MCF-7 breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sialylated IgG-activated integrin β4-Src-Erk axis stabilizes c-Myc in a p300 lysine acetyltransferase-dependent manner to promote colorectal cancer liver metastasis.Neoplasia (New York, N.Y.) · 2025Article
- MYC is in the CARDs: CBM complexes coordinate immune and MYC-dependent cellular function.Frontiers in molecular medicine · 2025Article
- Zhike Erfang Alleviates MRSA-Induced Pneumonia by Inhibiting TRAF6 and Activating NLRP3 Inflammatory Body.Journal of inflammation research · 2025Article
- Rapid increase of C/EBPα p42 induces growth arrest of acute myeloid leukemia (AML) cells by Cop1 deletion in Trib1-expressing AML.Leukemia · 2024Article
- RNA sequestration in P-bodies sustains myeloid leukaemia.Nature cell biology · 2024Article
- Sodium Houttuyniae attenuates ferroptosis by regulating TRAF6-c-Myc signaling pathways in lipopolysaccharide-induced acute lung injury (ALI).BMC pharmacology & toxicology · 2024Article
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
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Authors and funding
23 authors at 8 institutions in 1 country.
Tomoya MutoDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Maria GuillamotDepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
Jennifer YeungDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina College of Pharmacy, Columbia, SC 29208, USA.
Jing FangDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina College of Pharmacy, Columbia, SC 29208, USA.
Joshua BennettDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina College of Pharmacy, Columbia, SC 29208, USA.
Bettina NadorpDepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
Audrey LasryDepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
Luna Zea RedondoDepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
Kwangmin ChoiDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Yixiao GongDepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
Callum S WalkerDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Kathleen HuenemanDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Lyndsey C BolanosDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Laura BarreyroDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Lynn H LeeDivision of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Kenneth D GreisDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Nikita VasylievDepartment of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Alireza Khodadadi-JamayranApplied Bioinformatics Laboratories and Genome Technology Center, NYU School of Medicine, New York, NY 10016, USA.
Evgeny NudlerDepartment of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Amaia LujambioIcahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Scott W LoweDepartment of Cancer Biology and Genetics, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 201815, USA.
Iannis AifantisDepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA. Electronic address: ioannis.aifantis@nyulangone.org.
Daniel T StarczynowskiDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: daniel.starczynowski@cchmc.org.
Cincinnati Children's Hospital Medical Center · USNYU Langone’s Laura and Isaac Perlmutter Cancer CenterUniversity of South Carolina · USNew York University · USIcahn School of Medicine at Mount Sinai · USMemorial Sloan Kettering Cancer Center · USNew York Genome Center · USUniversity of Cincinnati Medical Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MLCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., KISSELA, BRETT M · 2015 to 2024
$37.5MENVIRONMETAL CARCINOGENESIS AND MUTAGENESIST32ES007250 · NIEHS · UNIVERSITY OF CINCINNATI · PI MILLER, WILLIAM E · 1988 to 2024
$11.9MTraining Program in Cancer TherapeuticsT32CA117846 · NCI · UNIVERSITY OF CINCINNATI · PI PRICE, CAROLYN M, TAKIAR, VINITA · 2006 to 2022
$6.5MRole of TET2 mutations in malignant transformation and acute myeloid leukemiaR01CA173636 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2013 to 2022
$6.3MXenotransplant and Genome Editing CoreU54DK126108 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Daniel Starczynowski, YI ZHENG · 2021 to 2026
$5.0MDecoding innate immune signaling in normal and myelodysplastic hematopoiesisR35HL135787 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI STARCZYNOWSKI, DANIEL · 2017 to 2022
$4.6MDissecting innate immune signaling in pre-leukemia evolutionR01CA271455 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI Iannis Aifantis, Daniel Starczynowski · 2022 to 2026
$3.2MTargeting an RNA Binding Protein Network in Acute Myeloid LeukemiaR01CA242020 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, AIFANTIS, IANNIS · 2020 to 2024
$2.7MmRNA stability and its impact on hematopoiesis and acute leukemiaR01CA266212 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Iannis Aifantis · 2022 to 2026
$2.7MRegulation of emergency hematopoiesis by the ubiquitin-proteasome systemR01HL159175 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI AIFANTIS, IANNIS, BUSINO, LUCA · 2021 to 2024
$2.5MThe cohesin complex as a tumor suppressor in myeloid leukemiaR01CA216421 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2017 to 2021
$2.5MNCATS NIH HHS UL1 TR001425NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA173636NCI NIH HHS R01 CA190261NCI NIH HHS R01 CA216421NCI NIH HHS R01 CA228135NCI NIH HHS R01 CA242020NCI NIH HHS R01 CA266212NCI NIH HHS R01 CA271455NCI NIH HHS T32 CA117846NHLBI NIH HHS F32 HL149280NHLBI NIH HHS L40 HL143713NHLBI NIH HHS R01 HL159175NHLBI NIH HHS R35 HL135787NIDDK NIH HHS R01 DK102759NIDDK NIH HHS R01 DK113639NIDDK NIH HHS U54 DK126108NIEHS NIH HHS T32 ES007250
Abstract
Clonal hematopoiesis (CH) is an aging-associated condition characterized by the clonal outgrowth of pre-leukemic cells that acquire specific mutations. Although individuals with CH are healthy, they are at an increased risk of developing myeloid malignancies, suggesting that additional alterations are needed for the transition from a pre-leukemia stage to frank leukemia. To identify signaling states that cooperate with pre-leukemic cells, we used an in vivo RNAi screening approach. One of the most prominent genes identified was the ubiquitin ligase TRAF6. Loss of TRAF6 in pre-leukemic cells results in overt myeloid leukemia and is associated with MYC-dependent stem cell signatures. TRAF6 is repressed in a subset of patients with myeloid malignancies, suggesting that subversion of TRAF6 signaling can lead to acute leukemia. Mechanistically, TRAF6 ubiquitinates MYC, an event that does not affect its protein stability but rather represses its functional activity by antagonizing an acetylation modification.
Indexed as
Leukemia, Myeloid, AcuteMyeloproliferative DisordersHematopoiesisHumansIntracellular Signaling Peptides and ProteinsMutationTNF Receptor-Associated Factor 6Intracellular Signaling Peptides and ProteinsTifab protein, humanTNF Receptor-Associated Factor 6AMLclonal hematopoiesishematopoiesisinflammationinnate immune signalingMDSMPNMYCmyeloid malignanciesTRAF6ubiquitination
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