We are focusing on the end of protein's life cycle, its death, which is essential for cell growth and development. Regulated protein destruction is mainly carried out by the proteasome, a multi-subunit protease that requires ubiquitin molecule as a ticket for entry. We employ multidisciplinary approaches to tackle the elusive mechanisms and crucial functions of ubiquitin-mediated proteolysis in vivo and in vitro. Key cellular regulators under our investigation include cell cycle kinase Mps1, tumor suppressor p53, prion protein PrP, misfolded protein CFTR. We have established unique angles and tools to unravel the function of proteolysis in cancer and age-related neurodegenerative diseases.
Cheng, H., Bao, X., Gan, X., Luo, S. and Rao, H (2017) Multiple E3s promote the degradation of Histone variant Cse4. Scientific Reports 7: 8565 | DOI:10.1038/s41598-017-08923-w
Cheng, H., Bao, X., and Rao, H (2016) The F box protein Rcy1 is involved in the degradation of Histone variant Cse4 and genome maintenance. J. Biol. Chem 291: 10372-10377.
Bao, X., Johnson, J., and Rao, H. (2015) Rad25 protein is targeted for degradation by the Ubc4-Ufd4 pathway. J. Biol. Chem 290, 8606-8612.
Krzeszinski JY, Choe V, Shao J, Bao X, Cheng H, Luo S, Huo K, Rao H. XPC promotes MDM2-mediated degradation of the p53 tumor suppressor. Mol Biol Cell. 2014 Jan;25(2):213-21.
Baek GH, Kim I, Rao H. The Cdc48 ATPase modulates the interaction between two proteolytic factors Ufd2 and Rad23. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13558-63.
Liu C, Choe V, Rao H. Genome-wide approaches to systematically identify substrates of the ubiquitin-proteasome pathway. Trends Biotechnol. 2010 Sep;28(9):461-7.
Kim I, Ahn J, Liu C, Tanabe K, Apodaca J, Suzuki T, Rao H. The Png1-Rad23 complex regulates glycoprotein turnover. J Cell Biol. 2006 Jan 16;172(2):211-9..
Rao H, Uhlmann F, Nasmyth K, Varshavsky A. Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability. Nature. 2001 Apr 19;410(6831):955-9.