Our research focuses on understanding how proteins are targeted by the ubiquitin-proteasome system (UPS)and how aberration of this system contributes to pathogenesis of diseases. Ubiquitination is a post-translational modification in which ubiquitin is covalently attached onto a substrate protein to alter the function and fate of the protein within the cell. It is a highly dynamic and regulatory process that governs nearly every fundamental cellular process, from cell cycle control, cell signaling, and stress response to regulation of protein stability and turnover. As such, deregulation of protein ubiquitination leads to a vast array of human diseases including cancers, immune disorders and neurodegenerative diseases. Understanding the mechanism and regulation of protein ubiquitination is therefore essential for elucidating the role of UPS in pathogenesis of these diseases and for the development of new strategies and therapeutics.
Egorova O , Sheng Y. (2014). A site-directed mutagenesis study of the MdmX RING
domain.Biochemical and Biophysical Research Communications. 447(4): 696-701.
Bohgaki M , Hakem A , Halaby MJ , Bohgaki T , Li Q , Bissey PA , Shloush J , Kislinger T , Sanchez O , Sheng Y , Hakem R. (2013). The E3 ligase PIRH2 polyubiquitylates CHK2 and regulates its turnover. Cell Death and Differentiation. 20(6)
Sarkari F , Wheaton K , La Delfa A , Mohamed M , Shaikh F , Khatun R , Arrowsmith CH , Frappier L , Saridakis V , Sheng Y. (2013). Ubiquitin-specific protease 7 is a regulator of ubiquitin-conjugating enzyme UbE2E1.The Journal of Biological Chemistry. 288(23)
Sheng Y , Hong JH , Doherty R , Srikumar T , Shloush J , Avvakumov GV , Walker JR , Xue S , Neculai D , Wan JW , Kim SK , Arrowsmith CH , Raught B , Dhe-Paganon S. (2012). A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen.Molecular & cellular proteomics : MCP. 11(8)
Hao Z , Duncan GS , Su YW , Li WY , Silvester J , Hong C , You H , Brenner D , Gorrini C , Haight J ,Wakeham A , You-Ten A , McCracken S , Elia A , Li Q , Detmar J , Jurisicova A , Hobeika E , Reth M ,Sheng Y , Lang PA , Ohashi PS , Zhong Q , Wang X, Mak TW. (2012). The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasis.The Journal of Experimental Medicine. 209(1)
Hakem A , Bohgaki M , Lemmers B , Tai E , Salmena L , Matysiak-Zablocki E , Jung YS, Karaskova J , Kaustov L , Duan S , Madore J , Boutros P , Sheng Y , Chesi M , Bergsagel PL , Perez-Ordonez B ,Mes-Masson AM , Penn L , Squire J , Chen X , Jurisica I , Arrowsmith C , Sanchez O , Benchimol S, Hakem R. (2011). Role of Pirh2 in mediating the regulation of p53 and c-Myc. PLoS Genetics. 7(11)