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Role of c-Myb in the regulation of natural killer cell activity

 Hee-Wook Shin  ;  Yoo-Jin Lee  ;  Jongsun Kim 
 Biochemical and Biophysical Research Communications, Vol.503(4) : 2807-2813, 2018 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Celastrol ; Interleukin-2 ; Natural killer cells ; Transforming growth factor-beta ; c-Myb
The regulation of natural killer (NK) cell activity is an important research goal for the development of immunotherapies. In this study, we identified transcription factors affecting NK cell activity. In particular, we screened transcription factors affected by interleukin-2 (IL-2) and transforming growth factor-beta (TGF-β) by protein/DNA arrays using primary NK cells. We found that celastrol, a c-Myb inhibitor, inhibited NK-92 cells more strongly than any other inhibitors of transcription factor candidates. In addition, c-Myb and c-Myb-related signaling molecules, e.g., Nemo-like kinase (NLK) and c-Myc, were regulated by the activation status of NK cells, suggesting that c-Myb is a key regulator of NK cell activity. We also found that celastrol inhibits NK-92-cell-mediated cytotoxicity via the downregulation of NKG2D and granzyme B. Knockdown studies also showed that c-Myb is important for NK cell activation. In particular, the knockdown of c-Myb did not significantly affect NK cell proliferation and survival but decreased the secretion of IFN-γ and the cytotoxicity of NK cells. Our data demonstrate that c-Myb plays a critical role in the activation of NK cells and therefore is a therapeutic target for cancer and viral diseases
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
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