Ubiquitin signaling in brain cancer Image Vincenzo D’Angiolella, MD, PhD, Charles and Ethel Barr Chair of Cancer Research\n Research in a Nutshell Proteins in cells are the machines that operate all the cellular functions. To operate efficiently proteins need to be cleared when they are not necessary and/or turned over when they are faulty. The Ubiquitin Proteasome System (UPS) is the main system responsible for the clearance of proteins in cells. The UPS operates by transferring multiple ubiquitin proteins in chains to residues of target proteins. The ubiquitin chains formed on the proteins are a signal of recognition by the proteasome which digests the protein ubiquitinated and recycles ubiquitin. The UPS makes up a large versatile system involved in regulating the majority of known biological processes. Dysregulation of UPS is often present in cancer. The mission of the laboratory is to decipher the role of the UPS in the pathogenesis and treatment response of brain cancers. Our long-term ambition is to develop novel drugs to improve brain cancers prognosis. The UPS represents a powerful endogenous cellular tool to destroy cancer proteins with targeted approaches. People Vincenzo D’Angiolella Group Leader Paul Smith Senior Research Fellow Varun Gopala-Krishna Research Fellow Xinhui Lan DPhil student Contact vdangio@ed.ac.uk Key Publications Chen Z, Ioris RM, Richardson S, Van Ess AN, Vendrell I, Kessler BM, Buffa FM, Busino L, Clifford SC, Bullock AN, D'Angiolella V. Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation. Cell Death Differ. 2022 Oct;29(10):1955-1969. doi: 10.1038/s41418-022-00983-4. Epub 2022 Apr 4. PMID: 35379950; PMCID: PMC9525703. Humphreys LM, Smith P, Chen Z, Fouad S, D'Angiolella V. The role of E3 ubiquitin ligases in the development and progression of glioblastoma. Cell Death Differ. 2021 Feb;28(2):522-537. doi: 10.1038/s41418-020-00696-6. Epub 2021 Jan11. PMID: 33432111; PMCID: PMC7862665. Fouad S, Wells OS, Hill MA, D'Angiolella V. Cullin Ring Ubiquitin Ligases (CRLs) in Cancer: Responses to Ionizing Radiation (IR) Treatment. Front Physiol. 2019 Oct 1;10:1144. doi: 10.3389/fphys.2019.01144. PMID: 31632280; PMCID: PMC6781834. Burdova K, Yang H, Faedda R, Hume S, Chauhan J, Ebner D, Kessler BM, Vendrell I, Drewry DH, Wells CI, Hatch SB, Dianov GL, Buffa FM, D'Angiolella V. E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. EMBO J. 2019 Oct 15;38(20):e101443. doi: 10.15252/embj.2018101443. Epub 2019 Aug 19. PMID: 31424118; PMCID: PMC6792013. D'Angiolella V, Donato V, Forrester FM, Jeong YT, Pellacani C, Kudo Y, Saraf A, Florens L, Washburn MP, Pagano M. Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell. 2012 May 25;149(5):1023-34. doi: 10.1016/j.cell.2012.03.043. PMID: 22632967; PMCID: PMC3616325. Full publication list can be found on Research Explorer: Vincenzo D'Angiolella — University of Edinburgh Research Explorer Collaborations Professor Steven Pollard, The University of Edinburgh Professor Francesca Buffa, Universita “La Bocconi”, Milano Professor Benedikt Kessler, The University of Oxford Professor Kristijan Ramadan, Lee Kong Chian School of Medicine (LKCMedicine) Professor Steve Clifford, University of Newcastle Partners and Funders Cancer Research UK Medical Research Council Oxford Science Enterprise (OSE) Scientific Themes Ubiquitin, medulloblastoma, glioblastoma, DNA repair This article was published on 2024-09-23
