SCILLS - The Scottish Institute for Cell Signalling

SCILLS is dedicated to the study of how biological processes are controlled and how they become deregulated in disease. The Protein Ubiquitination Unit is the Institute's first research Division. Its major aims are to advance understanding of the role of protein ubiquitination and related modifications in cell regulation and human disease, to facilitate the development of drugs to treat diseases caused by abnormalities in this process, to generate reagents and improve technologies on which more rapid progress in this area depends, and to train the next generation of scientists who will advance the subject.

Relevant recent publications

2009

Cohen, P. (2009). Keep nibbling at the edges. J. Biol. Chem. 284, pp. 23891-23901.

Smith, H., Peggie, M., Campbell, D.G., Vandermoere, F., Carrick, E and Cohen, P. (2009). Identification of the phosphorylaton sites on the E3 ubiquitin ligase Pellino that are critical for activation by IRAK1 and IRAK4. Proc. Natl. Acad. Sci. USA 106, pp. 4584-4590.

Clark, K., Peggie, M., Plater, L. and Cohen, P. (2009). Use of a pharmacological inhibitor to study the regulation and physiological roles of TBK1 and IKKe distinct upstream kinase mediates Ser172 phosphorylation and activation. J. Biol. Chem. 284, pp. 14136-14146 published on-line.

Cohen, P. (2009). Targeting protein kinases for the development of anti-inflammatory drugs. Current Opinion in Cell Biol. 21, pp. 317-324.

Geoffroy, M.C. and Hay, R.T. (2009). An additional role for SUMO in ubiquitin- mediated proteolysis. Nat. Rev. Mol. Cell Biol. May 28. [Epub ahead of print]

Golebiowski, F., Matic, I., Tatham, M.H., Cole, C., Yin, Y., Nakamura, A., Cox, J., Barton, G.J., Mann, M. and Hay RT. (2009). System-wide changes to SUMO modifications in response to heat shock. Science Signaling. May 26;2(72):ra24.

Shen, L.N., Geoffroy, M.C., Jaffray, E.G. and Hay RT. (2009). Characterization of SENP7, a SUMO-2/3-specific isopeptidase. Biochem. J. Jun 26; 421 (2), pp. 223-30.

Tatham, M.H. and Hay, R.T. (2009). FRET-based in vitro assays for the analysis of SUMO protease activities. Methods Mol. Biol. 497, pp. 253-68.

Meyer-Schaller, N., Chou, Y.C., Sumara, I., Martin, D.D., Kurz, T., Katheder, N., Hofmann, K., Berthiaume, L.G., Sicheri, F. and Peter. M. (2009). The human cn1-like protein DCNL3 promotes Cul3 neddylation at membranes. Proc. Natl. Acad. Sci. USA. Jul 14. [Epub ahead of print] PMID: 19617556 [PubMed - as supplied by publisher]

pubmed

Rosado, I.V., Niedzwiedz, W., Alpi, A.F., and Patel, K.J. (2009). The Walker B motif in avian FANCM is required to limit sister chromatid exchanges but is dispensable for DNA crosslink repair. Nuc. Acids. Res. 37(13), pp. 4360-4370.

Moser, S., von Elsner, S., Buessing, I., Alpi, A.F., Schnabel, R., and Gartner, A. (2009). Functional dissection of Caenorhabditis elegans CLK-2/TEL2 cell cycle defects during embryogenesis and germline development. PLOS Genetics 5(4).

Alpi, A.F., Patel K.J. (2009). Monoubiquitylation in the Fanconi anemia DNA damage response pathway. DNA Repair 8(4), pp. 430-435.

2008

Al-Hakim, A. K., Zagorska, A., Chapman, L., Deak, M., Peggie, M. and Alessi, D. R. (2008). Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains. Biochem. J. 411, pp. 249-60.

Windheim, M., Stafford, M., Peggie, M. and Cohen, P. (2008). IL-1 induces the Lys63-linked polyubiquitylation of IRAK1 to facilitate NEMO binding and the activation of IκBα kinase. Mol. Cell. Biol. 28, pp. 1783-1791.

Ordureau, A., Smith, H., Windheim, M., Peggie, M., Carrick, E., Vandermoere, F., Morrice, N.A. and Cohen, P. (2008). The IRAK-catalysed phosphorylation of Pellino isoforms activates their E3 ligase activity. Biochem. J. 409, pp. 43-52.

Mendoza, H., Campbell, D.G., Burness, K., Hastie, J. and Cohen, P. (2008). Identification of novel phosphorylation sites in the TAK1 complex. Biochem. J. 409, pp. 711-722.

Morton, S., Hesson, L., Peggie, M. and Cohen, P. (2008).Enhanced binding of TBK1 by an optineurin mutant that causes a familial form of primary open angle glaucoma. FEBS Lett. 582, pp. 997-1002.

Windheim, M., Peggie, M. and Cohen, P. (2008). Two different classes of E2 ubiquitin conjugating enzymes are required for the monoubiquitination of proteins and the elongation of polyubiquitin chains with a specific topology. Biochem. J. 409, pp. 723-729.

Kurz, T., Chou, Y.C., Willems, A.R., Meyer-Schaller, N., Hecht, M-L, Tyers, M., Peter, M. and Sicheri, F. (2008). Dcn1 functions as scaffold-type E3 ligase for cullin neddylation. Molecular Cell. 29, pp. 23-35.

Miles, W.O., Jaffray, E.G., Campbell, S.G., Takeda, S. , Bayston, L.J., Basu, S.P., Raftery, L.A., Ashe, M.P., Hay, R.T. and Ashe, H.L. (2008). Medea SUMOylation restricts the signalling range of the Dpp morphogen in the Drosophila embryo. Genes Dev. 22, pp. 2578-2590.

Tatham, M.H., Geoffroy, M.C., Shen, L., Plechanovova, A., Hattersley, N., Jaffray, E.G., Palvimo, J.J. and Hay, R.T. (2008). RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat. Cell Biol. 10, pp. 538-546.

Agostinho, M., Santos, V., Ferreira, F., Costa, R., Cardoso, J., Pinheiro, I., Rino, J., Jaffray, E., Hay, R.T. and Ferreira, J. (2008). Conjugation of human topoisomerase 2 alpha with small ubiquitin-like modifiers 2/3 in response to topoisomerase inhibitors: cell cycle stage and chromosome domain specificity. Cancer Res. 68, pp. 2409-2418.

Martin, S.F., Tatham, M.H., Hay, R.T. and Samuel, I.D. (2008). Quantitative analysis of multi-protein interactions using FRET: application to the SUMO pathway. Protein Sci. 17, pp. 777-784.

Xirodimas, D.P., Sundqvist, A., Nakamura, A., Shen, L., Botting, C. and Hay, R.T. (2008). Ribosomal proteins are targets for the NEDD8 pathway. EMBO Rep. 9, pp. 280-286.

Matic, I., van Hagen, M., Schimmel, J., Macek, B., Ogg, S.C., Tatham, M.H., Hay, R.T., Lamond, A.I., Mann, M., Vertegaal, A.C. (2008). In vivo identification of human small ubiquitin-like modifier polymerization sites by high accuracy mass spectrometry and an in vitro to in vivo strategy. Mol. Cell Proteomics. 7, pp. 132-144.

2007

Hay, R.T. (2007). SUMO-specific proteases: a twist in the tail. Trends Cell Biol. 17, pp. 370-376.

Tillmanns, S., Otto, C., Jaffray, E., Du Roure, C., Bakri, Y., Vanhill, L., Sarrazin, S., Hay, R.T. and Sieweke, M.H. (2007). SUMO modification regulates MafB-driven macrophage differentiation by enabling Myb-dependent transcriptional repression. Mol. Cell Biol. 27, pp. 5554-5564.

Jacobs, .AM., Nicol, S.M., Hislop, R.G., Jaffray, E.G., Hay, R.T. and Fuller-Pace, F.V. (2007). SUMO modification of the DEAD box protein p68 modulates its transcriptional activity and promotes its interaction with HDAC1. Oncogene 26, pp. 5866-76

Meinecke, I., Cinski, A., Baier, A., Peters, M.A., Dankbar, B., Wille, A., Drynda, A., Mendoza, H., Gay, R.E., Hay, R.T., Ink, B., Gay, S. and Pap, T. (2007). Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts. Proc. Natl. Acad. Sci. USA. 104, pp. 5073-5078.

Dorval, V., Mazzella, M.J., Mathews, P.M., Hay, R.T. and Fraser, P.E. (2007). Modulation of Abeta generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Biochem. J. 404, pp. 309-316.

Martin, S.F., Hattersley, N., Samuel, I.D., Hay, R.T. and Tatham, M.H. (2007). A fluorescence-resonance-energy-transfer-based protease activity assay and its use to monitor paralog-specific small ubiquitin-like modifier processing. Anal. Biochem. 363, pp. 83-90.

Janssen, K., Hofmann, T.G., Jans, D.A., Hay, R.T., Schulze-Osthoff, K. and Fischer, U. (2007). Apoptin is modified by SUMO conjugation and targeted to promyelocytic leukemia protein nuclear bodies. Oncogene 26, pp. 1557-1566.

Windheim, M., Lang, C., Peggie, M., Plater, L.A. and Cohen, P. (2007). Molecular mechanisms involved in the regulation of cytokine production by muramyl dipeptide. Biochem. J. 404, pp. 179-190.