TRAF6 functions as a tumor suppressor in myeloid malignancies by directly targeting MYC oncogenic activity Journal Article


Authors: Muto, T.; Guillamot, M.; Yeung, J.; Fang, J.; Bennett, J.; Nadorp, B.; Lasry, A.; Redondo, L. Z.; Choi, K.; Gong, Y.; Walker, C. S.; Hueneman, K.; Bolanos, L. C.; Barreyro, L.; Lee, L. H.; Greis, K. D.; Vasyliev, N.; Khodadadi-Jamayran, A.; Nudler, E.; Lujambio, A.; Lowe, S. W.; Aifantis, I.; Starczynowski, D. T.
Article Title: TRAF6 functions as a tumor suppressor in myeloid malignancies by directly targeting MYC oncogenic activity
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. © 2021 Elsevier Inc.
Keywords: inflammation; ubiquitination; hematopoiesis; myc; aml; mds; myeloid malignancies; clonal hematopoiesis; innate immune signaling; mpn; traf6
Journal Title: Cell Stem Cell
Volume: 29
Issue: 2
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2022-02-03
Start Page: 298
End Page: 314.e9
Language: English
DOI: 10.1016/j.stem.2021.12.007
PUBMED: 35045331
PROVIDER: scopus
PMCID: PMC8822959
DOI/URL:
Notes: Article -- Export Date: 1 March 2022 -- Source: Scopus
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  1. Scott W Lowe
    235 Lowe