The Sun laboratory is focused on understanding the molecular mechanisms involved in regulation of apoptosis, angiogenesis, and radioresistance by SCF E3 ubiquitin ligases and p53 signal pathways with the ultimate aim of identifying and validating targets for mechanism-driven, anti-cancer drug discovery.
SAG-SCF E3 ubiquitin ligases in regulation of apoptosis, carcinogenesis and angiogenesis
SAG (Sensitive to Apoptosis Gene, also known as RBX2 or ROC2) was cloned in the Sun laboratory. SAG forms active E3 ubiquitin ligases of SCF (Skp1, cullin1 and F-box protein) and VCB (VHL-Elongin-C/B) to promote the ubiquitination and degradation of a number of cellular critical proteins, such as p27, caspase-3, HIF-1α, c-Jun, and IkBα, thus regulating proliferation, apoptosis, hypoxia response, and carcinogenesis. SAG is over-expressed in non-small lung cell carcinoma, which correlates with poor prognosis. Physiological functions of SAG are being studied using constitutive knockout and conditional knockout mice.
RPS27L (Ribosomal Protein S27-Like) as a novel p53 target that regulates p53-induced apoptosis and genomic stability
RPS27L, a novel ribosomal-like gene, initially identified in the Sun laboratory as a p53-inducible gene from an genome profiling experiment. Further characterization of RPS27L revealed that it is a novel p53 target that mediates p53-induced apoptosis through inhibiting Mdm2. Physiological studies of RPS27L using constitutive and conditional knockout mouse models revealed its unexpected role in regulation of genomic stability.
Select Publications (from a total of 199)
- 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. Jan 16; 8:14002. doi: 10.1038/ncomms14002, 2017.
- Zhang Q, Karnak D, Tan M, Lawrence TS, Morgan MA, Sun Y: FBXW7 facilitates non-homologous 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(link is external))
- Li H, Tan M, Jia L, We, D, Zhao Y, Chen G, Xu J, Zhao L, Thomas D, Beer DG, and Sun Y: Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis. J Clin Invest. 124:835-846, 2014.
- Zha, Y, Xion, 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.
- 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.