Centre de Recherche
Ubiquitination of proteins is a post-translational modification required for a wide spectrum of biological functions, and defects in several processes involving ubiquitination underlie human diseases. The best characterized ubiquitination reaction involves the formation of polyubiquitin chains, leading to the degradation of target proteins by the proteasome. However, ubiquitination is a complex modification that also mediates cellular functions other than protein degradation. Protein modification by ubiquitin is a reversible reaction and specific proteases can remove the ubiquitin moiety. A vast repertoire of deubiquitinases (DUBs), including approximately 80 genes, are encoded by the human genome, and are emerging as important regulators of the ubiquitination-mediated processes. As the DUBs are largely unknown, establishing the biological functions and the molecular mechanisms of these proteases is not only a crucial step toward understanding ubiquitin-mediated signaling, but is also a fundamental aspect of cancer biology. We use functional genomics and proteomics approaches to determine the functions and mechanisms of action of DUB enzymes. Our investigations are primarily on DUB genes that are important for the expression and stability of the genome.
- Daou, N Mashtalir, I Hammond-Martel, H Pak, H Yu, G Sui, TM. Kristie and EB Affar. Crosstalk Between O-GlcNAcylation And Proteolytic Cleavage Regulates The HCF-1 Maturation Pathway. Proc Natl Acad Sci., 2011;108(7):2747-52
- I Hammond-Martel, H Pak, H Yu, R Rouget, AA Horwitz, JD. Parvin, EA. Drobetsky and EB Affar. PI 3 Kinase Related Kinases-Independent Proteolysis of BRCA1 Regulates Rad51 Recruitment During Genotoxic Stress in Human Cells. PlosONE 10.1371/journal.pone.0014027 (2010).
- H Yu, N Mashtalir, S Daou, I Hammond-Martel, J Ross, G Sui, GW. Hart, FJ Rauscher III, EA Drobetsky, E Milot, Y Shi and EB Affar. The Ubiquitin Carboxyl Hydrolase BAP1 Forms a Ternary Complex with YY1 and HCF-1 and is a Critical Regulator of Gene Expression. Mol. Cell. Biol.30(21):5071-85, (2010). Raphael Rouget , Yannick Auclair, Martin Loignon, El Bachir Affar, Elliot Drobetsky. A sensitive flow cytometry-based nucleotide excision repair assay unexpectedly reveals that mitogen-activated protein kinase signalling does not regulate the removal of UV-induced DNA damage in human cells. Journal of Biological Chemistry, 283(9):5533-5541, (2008).
- Andrew A. Horwitz, El Bachir Affar, George F. Heine, Yang shi, Jeffrey D. Parvin. A novel mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase. Proc. Natl. Acad. Sci., 104(16):6614-6619, (2007).
- Yu May Ma, Emmanuel Boucrot, Judit Villen, El Bachir Affar, Steven P. Gygi, Heinrich G. Gottlinger and Tomas Kirchhausen. Targeting of AMSH to endosomes is required for EGF receptor degradation. Journal of Biological Chemistry, 282(13):9805-9812, (2007).
- El Bachir Affar, Margaret Po-shan Luke, Frédérique Gay, Dominica Calvo, Guangchao Sui, Robert S. Weiss, En Li, and Yang Shi. Targeted Ablation of Par-4 Reveals a Cell-Type Specific Susceptibility To Apoptosis-Inducing Agents. Cancer Research, 66(7):3456-3462, (2006)
- El Bachir Affar*, Frédérique Gay*, Yujiang Shi, Huifei Liu, Maite Huarte, Su Wu, Collins Tucker, En Li, and Yang Shi. Essential dosage-dependent functions of the transcription factor Yin Yang 1 in late embryonic development and cell cycle progression. Molecular and Cellular Biology, 26(9):3565-3581, (2006). * Equal Contribution.
- Sang Ki Park, Minh Dang Nguyen, André Fisher, Margaret Po-Shan Luke, El Bachir Affar, Paul B. Dieffenbach, Huang-Chun Tseng, Yang Shi and Li-Huei Tsai. Par-4 links dopamine signaling and depression. Cell,122(2):275-287, (2005).
- Guangchao Sui, El Bachir Affar*, Yujiang Shi*, Chrystelle Brignone, Nathan R. Wall, Peng Yin, Mary Donohoe, Dominica Calvo, Margaret P. Luke, Steven R. Grossman, Yang Shi. Yin Yang 1 is a negative regulator of p53. Cell, 117(7): 859-872, (2004). * Equal contribution.
- Yujiang Shi, Jun-ichi Sawada, Guangchao Sui, El Bachir Affar, Johnathan R. Whetstine, Fei Lan, Hidesato Ogawa, Margaret Po-Shan Luke, Yoshihiro Nakatani and Yang Shi. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature, 422(6933):735-738, (2003).
- Guangchao Sui*, Christina Soohoo*, El Bachir Affar*, Frédérique Gay, Yujiang Shi, William Forrester and Yang Shi. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc. Natl. Acad. Sci., 99:5515-5520, (2002). * Equal Contribution.
- El Bachir Affar, Rashmi G. Shah, Annie K. Dallaire, Vincent Castonguay and Girish M. Shah. Role of poly(ADP-ribose) polymerase in rapid intracellular acidification induced by alkylating DNA damage. Proc. Natl. Acad. Sci., 99: 245-250, (2002).