Speaker：Prof. Yi Sun (Institute of Translational Medicine, Zhejiang University)
Title：SAG/RBX2 E3 Ubiquitin Ligase: From target identification to drug discovery
Time: June 02 (Friday) 2017, 16:00pm
Venue: Conference room 237, 2nd floor, Main building, KIZ
Everyone is welcome!
Introduction of Prof. Yi Sun
Research Areas
1）Cullin-RING ligase（CRL）intumorigenesis and its mechanism of action
2）The role of protein neddylationin tumorigenesis and its mechanism of action
3）Ribosomal protein S27-Like in tumorigenesis and genomic stability
Key Technologies
1) Conditional knockout mouse models and their use in tumorigenesis
2) Biochemical measurement of protein ubiquitylation and neddylation
3) Cell biology measurement of cell proliferation, apoptosis, autophagy and senescence
4) Gene overexpression and siRNA silencing
5) Histology and pathology
6) High-Throughput screening
Translational Potential
1) Small molecule inhibitors of E3 ubiquitin ligase as anticancer drugs
2) Small molecule inhibitors of neddylation as anticancer drugs
3) Identification of tumor biomarkers for early diagnosis and prognosis
Recent Publications
1. Zhang, Q., Karnak, D., Tan, M., Lawrence, T.S., Morgan, M.A., Sun, Y.: FBXW7 facilitates nonhomologous end-joining via K63-linked polyubiquitylation of XRCC4. Mol. Cell, 61: 419-433, 2016.http://dx.doi.org/10.1016/j.molcel.2015.12.010.
2. Wu, K., Chong, R. A., Yu, Q., Bai, J., Spratt, D. E., Ching, K., Lee, C., Miao, H., Zheng, N., Shaw, G. S., Sun, Y., Felsenfeld, D. P., Sanchez, R., Zheng, J.-N., and Pan., Z.-Q.: Suramin inhibits cullin-RING E3 ubiquitin ligases.Proc. Natl. Acad. Sci. USA.,113 (14) E2011-E2018, 2016.
3. Zhou, X. Tan, M., Nyati, M., Zhao, Y., Wang, G.X., and Sun, Y.: Blockage of neddylation modification stimulates tumor sphere formation in vitro, and stem cell differentiation and wound healing in vivo. Proc. Natl. Acad. Sci. USA.2016 May 24;113(21):E2935-2944. doi: 10.1073/pnas.1522367113. Epub 2016 May 9.
4. Lan, H., Tang, Z., Jin, H., and Sun, Y.: Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells. Sci Rep. 2016 Apr 11;6:24218. doi: 10.1038/ srep24218. PMID: 27063292.
5. Zhou, W., Xu, J., Li, H., Xu, M., Chen, Z.J.,Wei, W., Pan, Z., and Sun, Y.:Neddylation E2 UBE2F promotes the survival of lung cancer cells by activating CRL5 to degrade NOXA via the K11 linkage. Clinical Cancer Res. 2016 Sep 2. pii: clincanres.1585.2016. PMID:27591266; DOI:10.1158/1078-0432.CCR-16-1585
6. Xu, J., Zhou, W., Chen, G., Li, H., Zhao, Y., Liu, P., and Sun, Y.: The βTrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a novel tumor suppressor. Nature Communs, in press.
7. Kuang, P., Tan, M., Zhang, Q., and Sun, Y.: SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S E2s to ubiquitylate β-TrCP1 via K11-linkage for degradation. Scientific Reports, | 6:37441 | DOI: 10.1038/srep37441.
8. Tan, M., Xu, J., Feng, F., and Sun, Y.: Depletion of SAG/RBX2 E3 ubiquitin ligase suppresses prostate tumorigenesis via inactivation of the PI3K/AKT/mTOR axis. Mol. Cancer, Mol Cancer. 2016 Dec 12;15(1):81.PMID:27955654.
9. Zhou X#, Tan M#, Nyati MK, Zhao Y, Wang G*, Sun Y*. Blockage of neddylation modification stimulates tumor sphere formation in vitro and stem cell differentiation and wound healing in vivo. Proc Natl Acad Sci U S A. 2016, 113: E2935-2944.
10. Xie, C. M., Wei, D., Zhao, L., Marchetto, S., Mei, L., Borg,J.-P.,and Sun, Y.:Erbin is a novel substrate of Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis. J. Cell Biol, 209: 721-737, 2015.
11. Xiong, X.*, Zhao, Y.*, Tang, F., Thomas, D., Wang, X., Liu, Y., Zheng, P., and Sun, Y. Ribosomal protein S27-like is a physiological inhibitor of p53 that paradoxically suppresses tumorigenesis.eLife. Aug., 2014, http://dx.doi.org/10.7554/eLife.02236.
12. Li, H.*, Tan, M.*, Jia, L., Wei, D., Zhao, Y., Chen, G., Xu, J., Zhao, L., Thomas, D., Beer, D.G., and Sun, Y.: Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis. J. Clin. Invest. 2014 Feb 3;124(2):835-46. doi: 10.1172/JCI70297. Epub 2014 Jan 16.
13. Zhou, W., Wei, W. and Sun, Y.: Genetically engineered mouse models for functional studies of SCF E3 ubiquitin ligases. Cell Res., 23: 599-619, 2013.
14. Wei, D., Li, H., Yu, J., Sebolt, J. T., Zhao, L., Lawrence, T. S., Smith, P. G., Morgan, M. A., and Sun, Y. Radiosensitization of human pancreatic cancer cells by MLN4924, an investigational NEDD8-activating enzyme inhibitor. Cancer Res., 72: 282-293, 2012.
15. Tan, M*., Zhao, Y*., Kim, S., Liu, M., Jia, L., Saunders, T., Zhu, Y., and Sun, Y.: SAG/RBX2/ROC2 E3 ubiquitin ligase is essential for vascular and neural development by targeting NF1 for degradation. Dev. Cell, 21:1062-76, 2011.
16. Zhao, Y., Xiong, X., and Sun, Y.: DEPTOR, an mTOR inhibitor, is a physiological substrate of SCFβTrCP E3 ubiquitin ligase and regulates survival and autophagy. Mol. Cell, 44: 304-316, 2011.
Laboratory of Oncobiology
Laboratory of Tumor Signal Transduction
Key laboratory of Animal Models and Human Disease Mechanisms
05-25-2017
