Address421 E. Canfield Street, Suite 1146 Detroit, MI 48201
421 E. Canfield Street, Suite 1146
Detroit, MI 48201
• We use both Saccharomyces cerevisiae and mammalian systems to study the pathways that control the degradation of key regulatory proteins.
• We design peptide-based Protacs to target undruggable oncoproteins for proteasomal degradation.
• We develop novel approaches to targeting the proteasome for cancer therapy.
The focus of our research is to understand the molecular mechanisms underlying protein degradation mediated by the ubiquitin-proteasome system (UPS). UPS is the primary intracellular machine responsible for elimination of abnormal proteins and selective destruction of regulatory proteins involved in a wide range of cellular processes including cell cycle control, DNA transcription, replication and repair, and stress response. Dysregulation of UPS is implicated in various human diseases including cancer. Moreover, UPS has now become an important target for anti-cancer therapy. We use both Saccharomyces cerevisiae and mammalian systems to define the pathways that control the degradation of several key regulatory proteins. In addition, we are studying the differential responsees of normal cells and cancer cells to inhibitors of UPS.
Ju D, Li L, Xie Y. Homeostatic regulation of ribosomal proteins by ubiquitin-independent cotranslational degradation. Proc Natl Acad Sci U S A. 2023;120:e2306152120.
Wang H, Ju, D, Kho, D-H, Yang H. Li L, Raz A, Sun F, Xie Y. The ubiquitin specific protease USP34 protects the ubiquitin ligase gp78 from proteasomal degradation. Biochem Biophys Res Commun 2019;509:348-53.
Ha S-W, Ju D, Hao W, Xie Y. Rapidly translated polypeptides are preferred substrates for cotranslational protein degradation. J Biol Chem 2016;291:9827-34.
Ha S-W, Ju D, Xie Y Nuclear import factor Srp1 and its associated protein Sts1 couple ribosome-bound nascent polypeptides to proteasomes for cotranslational degradation. J Biol Chem 2014;289:2701-10.
Wang Y, Ha S-W, Zhang T, Kho D-H, Raz A, Xie Y. Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases. Oncotarget 2014;5:2044-51.
Xie Y. Feedback regulation of proteasome gene expression and its implications in cancer therapy. Cancer Metastasis Rev 2010;29: 687-93.
Xu H, Ju D, Jarois T, Xie Y. Diminished feedback regulation of proteasome expression and resistance to proteasome inhibitors in breast cancer cells. Breast Cancer Res Treat 2008;107:267-74.
PhD in Cell Biology (1996): University of Texas, MD Anderson Cancer Center, Houston, Texas
Post-Doc in Biochemistry (1996-2002): California Institute of Technology, Pasadena, California
CB7210 Fundamentals of Cancer Biology (Course Director)
CB7220 Molecular Biology of Cancer Development
CB7300 Special Topics F31 Grant Writing Course