Yi Sun

Yi Sun is an American scientist of Chinese origin. He is a molecular biologist and oncologist, and his research is focused on how altered protein Ubiquitylation and Neddylation contribute to cancer development. Sun is a Professor Emeritus of Radiation Oncology at the University of Michigan.

Sun is the Qiushi Chair Professor at the second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine in China. Sun has been a fellow of the American Association for the Advancement of Science since 2012.

Career and education In 1982, Sun obtained his M.D. degree at Jiangxi Medical College, Nanchang, China, and continued to Zhejiang University's School of Medicine, where he had his M.S. in biochemistry in 1985.

Sun then spent 8 years in Parke-Davis/Pfizer as research fellow for cancer target identification and drug discovery in Ann Arbor, Michigan.

SAG-CRLs regulates many important biological processes via targeting degradation of key proteins Sun and his team identified a number of key regulatory proteins as the substrates of CRLs that control a variety of important signal pathways and biological processes, particularly in growth and survival of cancer cells. These substrates include DEPTOR, XRCC4, SHOC2, SKP2, β-Catenin, MSX2, Nf1, c-Jun, IκBα, Erbin, NOXA, ASCT2, and DIRAS-2, as well as procaspase-3, HIF-1α, p27, MFN1, and EGR1. Targeted inhibition of CRLs causes accumulation of the tumor suppressors to inhibit cancer cell growth and cancer development.

Elucide neddylation function and discover neddylation inhibitors as novel anticancer agents Sun and his team showed a cross-talk between two neddylation E2s, and neddylation E2/E3 regulated the functions of immune cells. The team also found that E1 inhibitor MLN4924 sensitizes pancreatic cancer cells to radiation; regulates stem cell proliferation and differentiation; and strikingly suppressed tumorigenesis in the lung and pancreas, triggered by mutant KrasG12D as a single agent. The study in the lung tumorigenesis triggered an intensive collaboration with Takeda Pharmaceutics, Inc., leading to an investigator-initiated Phase II clinical trials of MLN4924 (also known as pevonedistat) plus Docetaxel in patients with previously treated advanced non-small cell lung cancer. In drug discovery side, Sun and his collaborators discovered small molecule inhibitors of neddylation E1, neddylation E2 UBE2F and UBE2M-DCN interactions.

Selected publications

Tan, M., Zhao, Y., Kim, S. J., Liu, M., Jia, L., Saunders, T. L., Zhu, Y., & Sun, Y. (2011). SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation. Developmental cell, 21(6), 1062–1076. https://doi.org/10.1016/j.devcel.2011.09.014 Zhao, Y., Xiong, X., & Sun, Y. (2020). Cullin-RING Ligase 5: Functional characterization and its role in human cancers. Seminars in cancer biology, 67(Pt 2), 61–79. https://doi.org/10.1016/j.semcancer.2020.04.003 Li, H., Tan, M., Jia, L., Wei, D., Zhao, Y., Chen, G., Xu, J., Zhao, L., Thomas, D., Beer, D. G., & Sun, Y. (2014). Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis. The Journal of clinical investigation, 124(2), 835–846. https://doi.org/10.1172/JCI70297 Zhao, Y., Xiong, X., & Sun, Y. (2011). DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Molecular cell, 44(2), 304–316. https://doi.org/10.1016/j.molcel.2011.08.029 Zhang, Q., Karnak, D., Tan, M., Lawrence, T. S., Morgan, M. A., & Sun, Y. (2016). FBXW7 Facilitates Nonhomologous End-Joining via K63-Linked Polyubiquitylation of XRCC4. Molecular cell, 61(3), 419–433. https://doi.org/10.1016/j.molcel.2015.12.010 Zhou, W., Xu, J., Tan, M., Li, H., Li, H., Wei, W., & Sun, Y. (2018). UBE2M Is a Stress-Inducible Dual E2 for Neddylation and Ubiquitylation that Promotes Targeted Degradation of UBE2F. Molecular cell, 70(6), 1008–1024.e6. https://doi.org/10.1016/j.molcel.2018.06.002 Zhang, S., You, X., Zheng, Y., Shen, Y., Xiong, X., & Sun, Y. (2023). The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells. The Journal of clinical investigation, 133(4), e162434. https://doi.org/10.1172/JCI162434 Zhou, Q#., Yu, H#., Chen, Y., Ren, J., Lu, Y., and Sun, Y. (2024) The CRL3KCTD10 ubiquitin ligase-USP18 axis coordinately regulates cystine uptake and ferroptosis by modulating SLC7A11. PNAS, 121(28):e2320655121. https://doi.org/10.1073/pnas.2320655121 Zhang, F. Wang, H., Xiong, X., Zhao, Y., and Sun, Y. (2025) RHEB neddylation by the UBE2F-SAG axis enhances mTORC1 activity and aggravates liver tumorigenesis. EMBO J., 44: 1185-1219. https://doi.org/10.1038/s44318-024-00353-5 Yin, L., Zhang, J., Zhu, Z., Peng, X., Lan, H., Ayoub, A., Tan, M., Zhou, B., He, Y., Wang, S., Lu, Y., Liu, W., Xiong, X., Huang, J., Dou, Y., Mao, F., and Sun, Y. (2025) The FBXW7-KMT2 axis in cancer-associated fibroblasts control the tumor growth via an epigenetic-paracrine mechanism. PNAS, 122(13):e2423130122. https://doi.org/10.1073/pnas.2423130122 Yu, Q., Zhang, S., Li, Z., Liang, T., and Sun, Y. (2026) SAG/RBX2/ROC2/RNF7 dual E3 ligase: From target identification, validation to drug discovery. BBA Reviews on Cancer, https://doi.org/10.1016/j.bbcan.2026.189546 Zhang, S., Lan, H., and Sun, Y. (2026) Protein neddylation as a therapeutic target: Challenges and Opportunities. J Clin Invest., 2026 Aug 3;136(15):e206924. https://doi.org/10.1172/jci206924