Centro Andaluz de Biología Molecular y Medicina Regenerativa

Ubiquitin (-like) signaling and Proteomics

We work in Ubiquitin and SUMO signalling in Genome biology related processes.

We do awesome science! More updated information coming soon!

More updated information coming soon!
More updated information coming soon!

We study the role of ubiquitin(-like) signaling in the regulation of Genome biology- and cancer-relevant E3 enzymes specific targets.

We use mass spectrometry-based proteomics tools to identify the specific substrates of E3 enzymes which have a role in genome biology. Misregulation of these E3 enzymes leads to the appearance of cancer. Furthermore, we employ cell biology, biochemistry, and molecular biology techniques to unravel the function that ubiquitin signaling has in the regulation of the activity of these ubiquitin target proteins.

Among others We apply it on ubiquitin ligases relevant in DNA repair and cancer. Particularly, this grant aims to identify the specific substrates for the BRCA1/BARD1 heterodimer, which deficiency is the first cause of hereditary breast and ovarian cancer. The role of the ubiquitin ligase activity of BRCA1/BARD1 in DNA repair and Cancer remains controversial.

Post translational modifications play a very important role in the fine tuning of protein function. These modifications can consist in the addition of small chemical groups or the covalent attachment of other small proteins. Among the small proteins that can be attached to other proteins, the most relevant one is ubiquitin.

Ubiquitination consists of a cascade reaction performed by the so called E1, E2 and E3 enzymes. More than 600 E3 enzymes are encoded in the human genome. In the lab, we combine mass-spectrometry based proteomics approaches to identify E3-specific ubiquitination substrates with molecular biology, biochemistry and cell biology techniques to unravel the role of ubiquitination on the regulation of these ubiquitinated proteins.

Ubiquitin signaling is involved in practically every single cellular process, having a very high importance in the organisational dynamics of the genome including the DNA damage response. The DNA damage response consists of the plethora of signaling pathways and enzymatic activities that cells are endorsed with in order to overcome the different sources of DNA damage that challenge the integrity of their genomes.

Ubiquitin signaling is involved in practically every single cellular process, having a very high importance in the organisational dynamics of the genome including the DNA damage response. The DNA damage response consists of the plethora of signaling pathways and enzymatic activities that cells are endorsed with in order to overcome the different sources of DNA damage that challenge the integrity of their genomes.

Deficiencies in the DNA damage response cause genome instability, which is one of the hallmarks of cancer.

The aim of our research is to discover new components of the DNA damage response machinery that could become targets of anti-cancer treatments in the future.

Projects as PI

  • UbiGap: Understanding under-replicated DNA gaps signaling and processing with a focus on ubiquitin. (EMERGIA20-00276) – Junta de Andalucía – Andalusian Regional Government.
  • Identification of BRCA/BARD1 ubiquitin E3 ligase target proteins to obtain novel insight in breast- and ovarían cancer (KWF-YIG 11367) – Dutch Cancer Foundation.

Scientific Articles:

  1. Salas-Lloret, D., Jansen, N.S., Nagamalleswari, E., van der Meulen, C., Gracheva, E., de Ru, A.H., Otte, H.A.M., van Veelen, P.A., Pichler, A., Goedhart, J., Vertegaal, A.C.O., González-Prieto, R.# (2023) SUMO-activated target traps (SATTs) enable the identification of a comprehensive E3-specific SUMO proteome. Sci Adv 9: eadh2073.

  2. Fan, C., Gonzalez-Prieto, R., Kuipers, T.B., Vertegaal, A.C.O., van Veelen, P.A., Mei, H., and Ten Dijke, P. (2023). The lncRNA LETS1 promotes TGF-beta-induced EMT and cancer cell migration by transcriptionally activating a TbetaR1-stabilizing mechanism. Sci Signal 16, eadf1947. 10.1126/scisignal.adf1947.
  3. Yalcin, Z., Koot, D., Bezstarosti, K., Salas-Lloret, D., Bleijerveld, O.B., Boersma, V., Falcone, M., Gonzalez-Prieto, R., Altelaar, M., Demmers, J.A.A., and Jacobs, J.J.L. (2023). Ubiquitinome profiling reveals in vivo UBE2D3 targets and implicates UBE2D3 in protein quality control. Molecular & cellular proteomics : MCP, 100548. 10.1016/j.mcpro.2023.100548.
  4. van den Heuvel, D., Kim, M., Wondergem, A.P., van der Meer, P.J., Witkamp, M., Lambregtse, F., Kim, H.S., Kan, F., Apelt, K., Kragten, A., …, Gonzalez-Prieto, R., …, et al. (2023). A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair. Proceedings of the National Academy of Sciences of the United States of America 120, e2208860120. 10.1073/pnas.2208860120.
  5. Tessier, S., Ferhi, O., Geoffroy, M.C., Gonzalez-Prieto, R., Canat, A., Quentin, S., Pla, M., Niwa-Kawakita, M., Bercier, P., Rerolle, D., et al. (2022). Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells. Nature communications 13, 5726. 10.1038/s41467-022-33147-6.
  6. Salas-Lloret, D., and Gonzalez-Prieto, R.# (2022). Insights in Post-Translational Modifications: Ubiquitin and SUMO. Int J Mol Sci 23. 10.3390/ijms23063281.
  7. Kumar, S., Schoonderwoerd, M.J.A., Kroonen, J.S., de Graaf, I.J., Sluijter, M., Ruano, D., Gonzalez-Prieto, R., Verlaan-de Vries, M., Rip, J., Arens, R., et al. (2022). Targeting pancreatic cancer by TAK-981: a SUMOylation inhibitor that activates the immune system and blocks cancer cell cycle progression in a preclinical model. Gut. 10.1136/gutjnl-2021-324834.
  8. Kamp, J.A., Lemmens, B., Romeijn, R.J., Gonzalez-Prieto, R., Olsen, J.V., Vertegaal, A.C.O., van Schendel, R., and Tijsterman, M. (2022). THO complex deficiency impairs DNA double-strand break repair via the RNA surveillance kinase SMG-1. Nucleic acids research 50, 6235-6250. 10.1093/nar/gkac472.
  9. Blessing, C., Apelt, K., van den Heuvel, D., Gonzalez-Leal, C., Rother, M.B., van der Woude, M., Gonzalez-Prieto, R., Yifrach, A., Parnas, A., Shah, R.G., et al. (2022). XPC-PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair. Nature communications 13, 4762. 10.1038/s41467-022-31820-4.
  10. van der Weegen, Y., de Lint, K., van den Heuvel, D., Nakazawa, Y., Mevissen, T.E.T., van Schie, J.J.M., San Martin Alonso, M., Boer, D.E.C., Gonzalez-Prieto, R., Narayanan, I.V., et al. (2021). ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation. Nature cell biology 23, 595-607. 10.1038/s41556-021-00688-9.
  11. van den Heuvel, D., Spruijt, C.G.*, Gonzalez-Prieto, R.*, Kragten, A., Paulsen, M.T., Zhou, D., Wu, H., Apelt, K., van der Weegen, Y., Yang, K., et al. (2021). A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair. Nature communications 12, 1342. 10.1038/s41467-021-21520-w.
  12. Singh, J.K., Smith, R., Rother, M.B., de Groot, A.J.L., Wiegant, W.W., Vreeken, K., D’Augustin, O., Kim, R.Q., Qian, H., Krawczyk, P.M.,… Gonzalez-Prieto, R.,… et al. (2021). Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining. Nature communications 12, 6560. 10.1038/s41467-021-26691-0.
  13. Koedoot, E., van Steijn, E., Vermeer, M., Gonzalez-Prieto, R., Vertegaal, A.C.O., Martens, J.W.M., Le Devedec, S.E., and van de Water, B. (2021). Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention. J Exp Clin Cancer Res 40, 82. 10.1186/s13046-021-01863-4.
  14. Goossens, R., Tihaya, M.S., van den Heuvel, A., Tabot-Ndip, K., Willemsen, I.M., Tapscott, S.J., Gonzalez-Prieto, R., Chang, J.G., Vertegaal, A.C.O., Balog, J., and van der Maarel, S.M. (2021). A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression. Sci Rep 11, 23642. 10.1038/s41598-021-03030-3.
  15. Gonzalez-Prieto, R.#, Eifler-Olivi, K., Claessens, L.A., Willemstein, E., Xiao, Z., Talavera Ormeno, C.M.P., Ovaa, H., Ulrich, H.D., and Vertegaal, A.C.O. (2021). Global non-covalent SUMO interaction networks reveal SUMO-dependent stabilization of the non-homologous end joining complex. Cell reports 34, 108691. 10.1016/j.celrep.2021.108691.
  16. Cano-Linares, M.I., Yanez-Vilches, A., Garcia-Rodriguez, N., Barrientos-Moreno, M., Gonzalez-Prieto, R., San-Segundo, P., Ulrich, H.D., and Prado, F. (2021). Non-recombinogenic roles for Rad52 in translesion synthesis during DNA damage tolerance. EMBO reports 22, e50410. 10.15252/embr.202050410.
  17. Cabello-Lobato, M.J., Gonzalez-Garrido, C., Cano-Linares, M.I., Wong, R.P., Yanez-Vilchez, A., Morillo-Huesca, M., Roldan-Romero, J.M., Vicioso, M., Gonzalez-Prieto, R., Ulrich, H.D., and Prado, F. (2021). Physical interactions between MCM and Rad51 facilitate replication fork lesion bypass and ssDNA gap filling by non-recombinogenic functions. Cell reports 36, 109440. 10.1016/j.celrep.2021.109440.
  18. Apelt, K., White, S.M., Kim, H.S., Yeo, J.E., Kragten, A., Wondergem, A.P., Rooimans, M.A., Gonzalez-Prieto, R., Wiegant, W.W., Lunke, S., et al. (2021). ERCC1 mutations impede DNA damage repair and cause liver and kidney dysfunction in patients. J Exp Med 218. 10.1084/jem.20200622.
  19. van der Weegen, Y., Golan-Berman, H., Mevissen, T.E.T., Apelt, K., Gonzalez-Prieto, R., Goedhart, J., Heilbrun, E.E., Vertegaal, A.C.O., van den Heuvel, D., Walter, J.C., et al. (2020). The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II. Nature communications 11, 2104. 10.1038/s41467-020-15903-8.
  20. Liu, S., Gonzalez-Prieto, R., Zhang, M., Geurink, P.P., Kooij, R., Iyengar, P.V., van Dinther, M., Bos, E., Zhang, X., Le Devedec, S.E., et al. (2020). Deubiquitinase Activity Profiling Identifies UCHL1 as a Candidate Oncoprotein That Promotes TGFbeta-Induced Breast Cancer Metastasis. Clin Cancer Res 26, 1460-1473. 10.1158/1078-0432.CCR-19-1373.
  21. Sha, Z., Blyszcz, T., Gonzalez-Prieto, R., Vertegaal, A.C.O., and Goldberg, A.L. (2019). Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. The Journal of biological chemistry 294, 15218-15234. 10.1074/jbc.RA119.009147.
  22. Salas-Lloret, D., Agabitini, G., and Gonzalez-Prieto, R.# (2019). TULIP2: An Improved Method for the Identification of Ubiquitin E3-Specific Targets. Front Chem 7, 802. 10.3389/fchem.2019.00802.
  23. Gjonaj, L., Sapmaz, A., Gonzalez-Prieto, R., Vertegaal, A.C.O., Flierman, D., and Ovaa, H. (2019). USP7: combining tools towards selectivity. Chem Commun (Camb) 55, 5075-5078. 10.1039/c9cc00969h.
  24. Kumar, R.*, Gonzalez-Prieto, R.*, Xiao, Z.*, Verlaan-de Vries, M., and Vertegaal, A.C.O. (2017). The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery. Nature communications 8, 1809. 10.1038/s41467-017-01900-x.
  25. Gonzalez-Prieto, R.#, Cuijpers, S.A., Luijsterburg, M.S., van Attikum, H., and Vertegaal, A.C. (2015). SUMOylation and PARylation cooperate to recruit and stabilize SLX4 at DNA damage sites. EMBO reports 16, 512-519. 10.15252/embr.201440017.
  26. Gonzalez-Prieto, R.*, Cuijpers, S.A.*, Kumar, R., Hendriks, I.A., and Vertegaal, A.C. (2015). c-Myc is targeted to the proteasome for degradation in a SUMOylation-dependent manner, regulated by PIAS1, SENP7 and RNF4. Cell Cycle 14, 1859-1872. 10.1080/15384101.2015.1040965.
  27. Gonzalez-Prieto, R., Munoz-Cabello, A.M., Cabello-Lobato, M.J., and Prado, F. (2013). Rad51 replication fork recruitment is required for DNA damage tolerance. The EMBO journal 32, 1307-1321. 10.1038/emboj.2013.73.
  28. Martín-Banderas, L., González-Prieto, R., Rodríguez-Gil, A., Fernández-Arévalo, M., Flores-Mosquera, M., Chávez, S., and Gañán-Calvo, A.M. (2011). Application of Flow Focusing to the Break-Up of a Magnetite Suspension Jet for the Production of Paramagnetic Microparticles. Journal of Nanomaterials 2011, 1-10. 10.1155/2011/527437.
  29. Clemente-Ruiz, M., Gonzalez-Prieto, R., and Prado, F. (2011). Histone H3K56 acetylation, CAF1, and Rtt106 coordinate nucleosome assembly and stability of advancing replication forks. PLoS Genet 7, e1002376. 10.1371/journal.pgen.1002376.
  30. Gañán-Calvo, A.M., González-Prieto, R., Riesco-Chueca, P., Herrada, M.A., and Flores-Mosquera, M. (2007). Focusing capillary jets close to the continuum limit. Nature Physics 3, 737-742. 10.1038/nphys710.
  31. Ganan-Calvo, A.M., Martin-Banderas, L., Gonzalez-Prieto, R., Rodriguez-Gil, A., Berdun-Alvarez, T., Cebolla, A., Chavez, S., and Flores-Mosquera, M. (2006). Straightforward production of encoded microbeads by Flow Focusing: potential applications for biomolecule detection. International journal of pharmaceutics 324, 19-26. 10.1016/j.ijpharm.2006.05.032.


Book Chapters:

  1. Gonzalez-Prieto, R.#, Vertegaal, A.C.O.# (2019) Wilson, V. G. (ed.), SUMOylation and Ubiquitination: Current and Emerging Concepts. Caister Academic Press, U.K., pp.147-160.
  2. Gonzalez-Prieto, R., Cabello-Lobato, M.J., and Prado, F. (2021). In Vivo Binding of Recombination Proteins to Non-DSB DNA Lesions and to Replication Forks. Methods in molecular biology 2153, 447-458.

Group leader:
  • Román González Prieto
  • Dr. Carmen Espejo Serrano
PhD students:
  • Lourdes González Vinceiro
  • Emily Esperanza Soto Hidalgo