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

Tomoya Muto, Maria Guillamot, Jennifer Yeung, Jing Fang, Joshua Bennett, Bettina Nadorp, Audrey Lasry, Luna Zea Redondo, Kwangmin Choi, Yixiao Gong, Callum S. Walker, Kathleen Hueneman, Lyndsey C. Bolanos, Laura Barreyro, Lynn H. Lee, Kenneth D. Greis, Nikita Vasyliev, Alireza Khodadadi-Jamayran, Evgeny Nudler, Amaia LujambioScott W. Lowe, Iannis Aifantis, Daniel T. Starczynowski

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Pages (from-to)298-314.e9
JournalCell Stem Cell
Issue number2
StatePublished - 3 Feb 2022


  • AML
  • MDS
  • MPN
  • MYC
  • TRAF6
  • clonal hematopoiesis
  • hematopoiesis
  • inflammation
  • innate immune signaling
  • myeloid malignancies
  • ubiquitination


Dive into the research topics of 'TRAF6 functions as a tumor suppressor in myeloid malignancies by directly targeting MYC oncogenic activity'. Together they form a unique fingerprint.

Cite this