Bennett, Eric - University of California, San Diego

个人简介

Dr. Bennett received his PhD from Stanford University. He then carried out postdoctoral work at the Harvard Medical School.

研究领域

My lab is interested in understanding the fundamental principles of how proteins are destroyed within cells. The cellular environment must constantly adapt to changing conditions and one mechanistic strategy commonly employed is the targeted modification of proteins by ubiquitin chains and subsequent degradation by the proteasome. The ubiquitin-proteasome system (UPS) can be viewed as the cellular waste management system. The UPS is utilized as the cellular quality control system as it is tasked with the degradation of potentially toxic misfolded and misassembled proteins. The inability of the UPS to properly destroy these proteins has been linked to various human pathologies including amyotrophic lateral sclerosis (ALS, commonly referred to as Lou Gehrig's disease), Parkinson's disease, and many human cancers. Thus, understanding the mechanisms of how the UPS recognizes proteins to be destroyed and how the pathway becomes dysfunctional will be instrumental in understanding the etiology of these diseases. The lab uses integrated approaches to understand UPS activity coupling biochemistry, cell biology, and systems-level approaches. Deubiquitylating enzyme regulation The ubiquitylation of substrates occurs via a hierarchy of enzyme activity where ubiquitin activating enzymes (E1s) activate free ubiquitin and transfers the activated ubiquitin to ubiquitin conjugating enzymes, (E2s), who partner with ubiquitin ligases (E3s) to finally conjugate ubiquitin to substrates.

近期论文

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Harper JW, Bennett EJ. Proteome complexity and the forces that drive proteome imbalance. Nature. 2016 Sep 14;537(7620):328-38. PMID: 27629639 Arribas-Layton M, Dennis J, Bennett EJ, Damgaard CK, Lykke-Andersen J. The C-terminal RGG domain of human Lsm4 promotes processing body formation stimulated by arginine dimethylation. Mol Cell Biol. 2016 May 31 PMID: 27247266 Gendron JM, Webb K, Yang B, Rising L, Zuzow N, Bennett EJ. Using the ubiquitin-modified proteome to monitor distinct and spatially restricted protein homeostasis dysfunction. Mol Cell Proteomics. 2016 May 16. PMID: 27185884 Fu R, Olsen MT, Webb K, Bennett EJ, Lykke-Andersen J. Recruitment of the 4EHP-GYF2 cap-binding complex to tetraproline motifs of tristetraprolin promotes repression and degradation of mRNAs with AU-rich elements. RNA. 2016 Mar;22(3):373-82. PMID: 26763119 Higgins R, Gendron JM, Rising L, Mak R, Webb K, Kaiser SE, Zuzow N, Riviere P, Yang B, Fenech E, Tang X, Lindsay S, Christianson JC, Hampton RY, Wasserman SA, Bennett EJ. The unfolded protein response triggers site-specific regulatory ubiquitylation of 40S ribosomal proteins. Mol Cell. 2015 Jul 2;59(1):35-49. PMID: 26051182 Erickson SL, Corpuz EO, Maloy JP, Fillman C, Webb K, Bennett EJ, Lykke-Andersen J. A competition between decapping complex formation and ubiquitin-mediated proteasomal degradation controls human Dcp2 decapping activity. Mol Cell Biol. 2015 Apr 13.PMID: 25870104 Facette MR, Park Y, Sutimantanapi D, Luo A, Cartwright HN, Yang B, Bennett EJ, Sylvester AW, Smith LG. The SCAR/WAVE complex polarizes PAN receptors and promotes division asymmetry in maize. Nat Plants. 2015 Jan 26;1:14024. PMID: 27246760 Lyumkis D, Oliveira dos Passos D, Tahara EB, Webb K, Bennett EJ, Vinterbo S, Potter CS, Carragher B, Joazeiro CA. Structural basis for translational surveillance by the large ribosomal subunit-associated protein quality control complex. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):15981-6. PMID: 25349383 Ikeuchi Y, Dadakhujaev S, Chandhoke AS, Huynh MA, Oldenborg A, Ikeuchi M, Deng L, Bennett EJ, Harper JW, Bonni A, Bonni S. TIF1gamma Regulates Epithelial Mesenchymal Transition by Operating as a SUMO E3 Ligase for theTranscriptional Regulator SnoN1. J Biol Chem. 2014 Sep 5;289(36):25067-78. PMID: 25059663 Lykke-Andersen J, Bennett EJ. Protecting the proteome: Eukaryotic cotranslational quality control pathways.J Cell Biol. 2014 Feb 17;204(4):467-76. PMID: 24535822 Mejia LA, Litterman N, Ikeuchi Y, de la Torre-Ubieta L, Bennett EJ, Zhang C, Harper JW, Bonni A. A novel Hap1-Tsc1 interaction regulates neuronal mTORC1 signaling and morphogenesis in the brain. J Neurosci. 2013 Nov 13;33(46):18015-21. PMID: 24227713 Ziemba A, Hill S, Sandoval D, Webb K, Bennett EJ, Kleiger G. Multimodal mechanism of action for the Cdc34 acidic loop: a case study for why ubiquitin-conjugating enzymes have loops and tails. J Biol Chem. 2013 Nov 29;288(48):34882-96. PMID: 24129577 Tan MK, Lim HJ, Bennett EJ, Shi Y, Harper JW. Parallel SCF Adaptor Capture Proteomics Reveals a Role for SCFFBXL17 in NRF2 Activation via BACH1 Repressor Turnover. Molecular Cell 2013 Sep 10. PMID: 24035498 Zhang C, Mejia LA, Huang J, Valnegri P, Bennett EJ, Anckar J, Jahani-Asl A, Gallardo G, Ikeuchi Y, Yamada T, Rudnicki M, Harper JW, Bonni A. The X-linked intellectual disability protein PHF6 associates with the PAF1 complex and regulates neuronal migration in the mammalian brain. Neuron 2013 Jun 19;78(6):986-93. PMID: 23791194 Carrano AC, Bennett EJ. Using the ubiquitin modified proteome to monitor protein homeostasis function. Mol Cell Proteomics 2013 May 23. PMID: 23704779 Armour SM, Bennett EJ, Braun CR, Zhang XY, McMahon SB, Gygi SP, Harper JW, Sinclair DA. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex. Mol Cell Biol. 2013 Apr;33(8):1487-502. PMID: 23382074 Monda JK, Scott DC, Miller DJ, Lydeard J, King D, Harper JW, Bennett EJ, Schulman BA. Structural Conservation of Distinctive N-terminal Acetylation-Dependent Interactions across a Family of Mammalian NEDD8 Ligation Enzymes. Structure 2013 Jan 8;21(1):42-53. PMID: 23201271 Christianson JC*, Olzmann JA*, Shaler TA, Sowa ME, Bennett EJ, Richter CM, Tyler RE, Greenblatt EJ, Harper JW, Kopito RR. Defining Human ERAD Networks through an Integrative Mapping Strategy. Nature Cell Biology 2011 Nov 27;14(1):93-105. PMID: 22119785 *Authors contributed equally Scott DC, Monda JK, Bennett EJ, Harper JW, Schulman BA. N-Terminal Acetylation Acts as an Avidity Enhancer Within an Interconnected Multiprotein Complex. Science 2011 Nov 4;334(6056): 674-8. PMID: 21940857 Kim W*, Bennett EJ*, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, and Gygi SP. Systematic and quantitative assessment of the ubiquitin modified proteome Molecular Cell 2011 Oct 1;44(2):325-40. PMID: 21906983 *Authors contributed equally Bennett EJ, Rush J, Gygi SP, Harper JW. Dynamics of cullin-RING ubiquitin ligase assembly revealed by systematic quantitative proteomics. Cell 2010 Dec 10;143(6):951-965. Bennett EJ, Harper JW. Ubiquitin gets CARDed. Cell. 2010 Apr 16;141(2):220-222. Bennett EJ, Sowa ME, Harper JW. Cellular regulation by deubiquitinating enzymes. Nat. Rev. Mol Cell Bio. 2010 Feb Poster insert.