Regulation of the proteasome – Bernat Crosas

Principal investigator

Bernat Crosas obtained his degree in Biology at University of Barcelona (UB), and his PhD at the university autonomous of Barcelona (UAB), on oxidoreductases active with ethanol and retinoids. In 2001, he joined Dr. Finley lab, at the Department of Cell Biology of Harvard Medical School, working on proteasome regulation. In 2005, he obtained a Ramon y Cajal contract to join the IBMB, at Dr. Thomson lab, at the IBMB, where he developed projects on regulation of proteasome substrate receptors.

In 2009, he obtained a CSIC scientist researcher position. His lab is focused on uncovering novel levels of regulation of proteasome function and on the development of new drug, in collaboration with the Research Unit of Bioactive Molecules (RUBAM), at the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC).

Bijlmakers, M.J., Teixeira, J.,M., Boer, R., Mayzel, M., Puig-Sàrries, P., Karlsson, G., Coll, M., Pons, M., Crosas B. (2016). A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125. Scientific Reports 6:29232. doi: 10.1038/srep29232

Isasa, M., Suñer, C., Díaz, M., Puig-Sàrries, P., Zuin, A., Bichmann, A, Gygi, S,P,, Rebollo, E., Crosas, B. (2016). Cold Temperature Induces the Reprogramming of Proteolytic Pathways in Yeast. Journal of Biological Chemistry 291(4):1664-75. doi: 10.1074/jbc.M115.698662

Zuin, A., Bichmann, A., Isasa, M., Puig-Sàrries, P., Díaz, L.M., Crosas, B. (2015). Rpn10 monoubiquitination orchestrates the association of the ubiquilin-type DSK2 receptor with the proteasome. Biochemical Journal. 472(3):353-365. doi: 10.1042/BJ20150609

Puig-Sàrries, P., Bijlmakers, M.J., Zuin, A., Bichmann, A., Pons, M., Crosas, B. (2015) An intrinsically disordered region of RPN10 plays a key role in restricting ubiquitin chain elongation in RPN10 monoubiquitination. Biochemical Journal. 469(3):455-467. doi: 10.1042/BJ20141571

Crosas. B. (2014). Deubiquitinating enzyme inhibitor and their potencial in cance therapy. Current Cancer Drug Targets 14(6), 506-516. doi: 10.2174/1568009614666140725090620

Zuin, A., Isasa, M., Crosas, B. (2014) “Ubiquitin signaling: extreme conservation as a source of Diversity” Cells, 3, 690-701. doi: 10.3390/cells3030690

Hernández-Ortega S, Bru S, Ricco N, Ramírez S, Casals N, Jiménez J, Isasa M, Crosas B, Clotet J. (2013) Defective in mitotic arrest 1 (Dma1) ubiquitin ligase controls G1 cyclin degradation. Journal of Biological Chemistry 288, 4704-4714. doi: 10.1074/jbc.M112.426593

Isasa, M., Zuin, A., and Crosas, B. (2012) “Integration of multiple ubiquitin signals in proteasome regulation”. Methods in Molecular Biology 910, 337-70. doi: 10.1007/978-1-61779-965-5_15

Isasa, M., Katz., E.J., Kim, W., Yugo, V., González., S., Kirkpatrick, D.S., Thomson, T.M., Finley., S., Gygi, S.P. and Crosas, B*. (2010) Monoubiquitination of rpn10 regulates substrate recruitment to the proteasome. Molecular Cell, 38(5), 733-745. Cover and preview. doi: 10.1016/j.molcel.2010.05.001

Katz., E.J., Isasa, M., and Crosas, B* (2010) A new map to understand deubiquitination. Biochemical Society Transactions, 38(Pt 1): 21-8. doi: 10.1042/BST0380021

Crosas, B.*, Farràs, R., Marfany, G., Rodríguez, M. and Thomson, T.M*. Searching for the boundaries: unlimited expansion of ubiquitin and ubiquitin-like signals in multiple cellular functions (2010) Biochemical Society Transactions, 38(Pt 1): 1-5. doi: 10.1042/BST0380001

Crosas, B., Hanna, J., Kirkpatrick, D.S., Zang, P.,Tone, Y., Hathaway, N.A., Buecker, C., Leggett, D.S., Schmidt, M., King, R.W., Gygi, S.P. and Finley, D. (2006) Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell 127, 1401-1413. doi: 10.1016/j.cell.2006.09.051

Hanna, J., Hathaway, N.A., Tone, Y., Crosas, B., Elsasser, S., Kirkpatrick, D.S. Leggett, D.S., Gygi, S.P., King, R.W., and Finley, D. (2006) Deubiquitinating Enzyme Ubp6 Functions Noncatalytically to Delay Proteasomal Degradation. Cell, 127, 99-111. doi: 10.1016/j.cell.2006.07.038

Shang, F., Deng, G., Liu, Q., Guo, W., Haas, A.L., Crosas, B., Finley, D., Taylor, A. (2005) LYS-6-modified ubiquitin inhibits ubiquitin-dependent protein degradation. Journal of Biological Chemistry, 280, 20365-20374. doi: 10.1074/jbc.M414356200

Schmidt, M., Haas, W., Crosas., B., Santamaria, P.G., Gygi, S.P., Walz. A, Finley, D. (2005) The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle. Nature Structural & Molecular Biology, 12, 294-303. doi: 10.1038/nsmb914

Janse^, D.M., Crosas, B., Finley, D., Church, G.M. (2004) Localization to the Proteasome is Sufficient for Degradation. Journal of Biologial Chemistry. 279 (20): 21415-21420. doi: 10.1074/jbc.M402954200

Crosas, B., Hyndman, D.J., Gallego, O., Martras, S., Parés, X., Flynn, T.G., Farrés, J. (2003) Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism. Biochemical Journal 373 (3): 973-979. doi: 10.1042/bj20021818

Leggett, D.S., Hanna, J., Borodovsky, A., Crosas, B., Schmidt, M., Baker, R.T., Walz, T., Ploegh, H., Finley, D. (2002) Multiple associated proteins regulate proteasome structure and function. Molecular Cell 10 (3): 495-507. doi: 10.1016/S1097-2765(02)00638-X

Hirschberg, D., Cederlund, E., Crosas, B., Jonsson, A., Tryggvason, S., Farrés, J., Parés, X., Bergman, T., Jornvall, H. (2001) N-terminal acetylation in a third protein family of vertebrate alcohol dehydrogenase/retinal reductase found through a ‘proteomics’ approach in enzyme characterization. Cellular and Molecular Life Sciences 58 (9):1323-1326. doi: 10.1007/PL00000942

Crosas, B., Cederlund, E., Torres, D., Farrés, J., Jörnvall, H. and Parés, X. (2001) A vertebrate aldo­keto reductase active with retinoids and ethanol. Journal of Biological Chemistry 276 (22): 19132-19140. doi: 10.1074/jbc.M010478200

Allali-Hassani, A., Crosas, B., Martínez, S.E., Martras, S., Persson, B., Jörnvall, H., Parés, X. and Farrés, J. (2001) Kinetic effects of a single-amino acid mutation in a highly variable loop (residues 114 to 120) of class IV ADH. Chemico-Biological Interactions 130-132, 435-444. doi: 10.1016/S0009-2797(00)00288-X

Crosas, B., Allali-Hassani, A., Martínez, S.E., Martras, S., Persson, B., Jörnvall, H., Parés, X. and Farrés, J. (2000) Molecular basis for differential substrate specificity in class IV alcohol dehydrogenase: A conserved function in retinoid metabolism but not in ethanol oxidation. Journal of Biological Chemistry 275 (33): 25180-25187. doi: 10.1074/jbc.M910040199

Borràs, E., Coutelle, C., Rosell, A., Fernàndez-Muixí, F., Broch, M., Crosas, B., Hjelmqvist, L., Lorenzo, A., Gutiérrez, C., Santos, M., Szczepanek, M., Heilig, M., Quattrocchi, P, Farrés, J., Vidal, F., Richart, C., Mach, T., Bogdal, J., Jörnvall, H., Seitz, H. K., Couzigou, P. and Parés, X. (2000) Genetic polymorphisms of alcohol dehydrogenase in Europeans. ADH2 *2 allele decreases the risk for alcoholism and is associated with ADH3 *1. Hepatology 31 (4): 984-989. doi: 10.1053/he.2000.5978

Fernández, M.R., Biosca, J.A., Torres, D., Crosas, B. and Parés, X. (1999) A double residue substitution in the coenzyme binding site accounts for the different kinetic properties between yeast and human formaldehyde dehydrogenases. Journal of Biological Chemistry 274 (53): 37869-37875. doi: 10.1074/jbc.274.53.37869

Peralba, J.M., Cederlund, E., Crosas, B., Moreno, A., Julià, P., Martínez, S.E., Hjelmqvist, L., Persson, B., Farrés, J., Parés, X., Jörnvall, H. (1999) Structural and enzymatic properties of a gastric NAPD(H)-dependent and retinal-active alcohol dehydrogenase. Journal of Biological Chemistry 274 (37): 26021-26026. doi: 10.1074/jbc.274.37.26021

Peralba, J.M., Crosas, B., Moreno, A., Martínez, S.E., Julià, P., Farrés, J., Parés, X. (1999) Amphibian alcohol dehydrogenase. Purification and characterization of classes I and III from Rana perezi. Advances in Experimental Medicine and Biology 463: 343-350. doi: 10.1007/978-1-4615-4735-8_42

Farrés, J., Moreno, A., Crosas, B., Cederlund, E., Peralba, J.M., Allali-Hassani, A., Hjelmqvist, L., Jörnvall, H., Parés, X. (1994) Human and rat class IV alcohol dehydrogenase: correlation of primary structure with enzymatic properties. Advances in Experimental Medicine and Biology 372: 331-339. doi: 10.1007/978-1-4615-1965-2_40

Farrés, J., Moreno, A., Crosas, B., Peralba, J.M., Allali-Hassani, A., Hjelmqvist, L., Jörnvall, H. and Parés, X. (1994) Alcohol dehydrogenase of class IV (ss-ADH) from human stomach. cDNA sequence and structure/function relationship. European Journal of Biochemistry 224, 549-557. doi: 10.1111/j.1432-1033.1994.00549.x