한빛사논문
- 조회895
Wansang Cho[a]+, Solchan Won[b][e]+, Yoona Choi[a], Sihyeong Yi[a], Jong Beom Park[a], Jun-Gyu Park[b][e], Caroline E. Kim[a], Chintam Narayana[a], Ju Hee Kim[d], Junhyeong Yim[c], Young Il Choi[d], Dong-Sup Lee[b][e]*, and Seung Bum Park[a][c][d]*
[a]Dr. W. Cho, Dr. Y. Choi, S. Yi, J. B. Park, C. E. Kim, Dr. C. Narayana, and Prof. S. B. Park
Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul 08826, Korea
[b]S. Won, Dr. J.–G. Park, and Prof. D.–S. Lee
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
[c]J. Yim, and Prof. S. B. Park
Department of Biophysics and Chemical Biology, Seoul National University, Seoul 08826, Korea
[d]J. H. Kim, Dr. Y. I. Choi, and Prof. S. B. Park
SPARK Biopharma, Inc., Seoul 08791, Korea
[e]S. Won, Dr. J.–G. Park, and Prof. D.–S. Lee
Department of Biomedical Sciences, Wide River Institute of Immunology, Seoul National University College of Medicine, Seoul 03080, Korea
+These authors contributed equally.
*CORRESPONDING AUTHOR : Dong-Sup Lee, Seung Bum Park
Abstract
Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING–TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.
논문정보
- Research article
- 2023년 02월 (BRIC 등록일 2023-03-06)
- 국내 연구진
- 생명과학 > 분자생물학
관련 보도자료
- Bio통신원
- 2023. 03. 17
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