Investigating the essential roles of Ubiquitin-like molecules and the Ubiquitin Proteasome System

Alfred Vertegaal

Education

  • 2001: PhD in Medicine at the Leiden University, the Netherlands.
  • 1996: MSc in Biomedical Sciences at the Leiden University, the Netherlands.

Research Appointments

  • 2011: Associate Professor at the Leiden University Medical Center, the Netherlands.
  • 2008: Assistant Professor at the Leiden University Medical Center, the Netherlands.
  • 2004: Senior Scientist at Leiden University Medical Center, the Netherlands.
  • 2001: Dutch Cancer Society Postdoctoral Fellow at the Wellcome Trust Biocentre, Dundee, UK.
Alfred Vertegaal

Research Interests

We are interested in protein modification by Small Ubiquitin-like Modifiers (SUMOs). These modifiers are essential to maintain genome integrity and play critical roles in all nuclear processes. Furthermore, we interested in crosstalk between SUMOylation and other post-translational modifications.

We are using quantitative proteomics approaches to study SUMOylation at a system-wide level. Recently, we have developed site-specific methodology to directly identify SUMO conjugation sites on endogenous target proteins.

Selected individual SUMO target proteins are studied in detail. SUMOylation impaired mutants are generated and compared to wild-type forms to determine how SUMOylation regulates the activity of these proteins.

Selected Publications

Vertegaal,A.C. (2011). Uncovering ubiquitin and ubiquitin-like signaling networks. Chem. Rev. 111, 7923-7940.

Matic,I., Schimmel,J., Hendriks,I.A., van Santen,M.A., van de Rijke,F., van Dam,H., Gnad,F., Mann,M. and Vertegaal,A.C. (2010). Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif. Mol. Cell 39, 641-652.

van Hagen,M., Overmeer,R.M., Abolvardi,S.S., and Vertegaal,A.C. (2010). RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2alpha. Nucleic Acids Res. 38, 1922-1931.

Schimmel,J., Balog,C.I., Deelder,A.M., Drijfhout,J.W., Hensbergen,P.J., and Vertegaal,A.C. (2010). Positively charged amino acids flanking a sumoylation consensus tetramer on the 110kDa tri-snRNP component SART1 enhance sumoylation efficiency. J. Proteomics 73, 1523-1534.

Brouwer,A.K., Schimmel,J., Wiegant,J.C., Vertegaal,A.C., Tanke,H.J., and Dirks,R.W. (2009). Telomeric DNA mediates de novo PML body formation. Mol. Biol. Cell 20, 4804-4815.

Matic,I., van Hagen,M., Schimmel,J., Macek,B., Ogg,S.C., Tatham,M.H., Hay,R.T., Lamond,A.I., Mann,M., and 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, 132-144.

Roukens,M.G., Alloul-Ramdhani,M., Vertegaal,A.C., Anvarian,Z., Balog,C.I., Deelder,A.M., Hensbergen,P.J., and Baker,D.A. (2008). Identification of a new site of SUMOylation on Tel (ETV6) uncovers a PIAS-dependent mode of regulating Tel function. Mol. Cell Biol. 28, 2342-2357.

Schimmel,J., Larsen,K.M., Matic,I., van Hagen,M., Cox,J., Mann,M., Andersen,J.S., and Vertegaal,A.C. (2008). The ubiquitin-proteasome system is a key component of the SUMO-2/3 cycle. Mol. Cell Proteomics 7, 2107-2122.

Vertegaal,A.C., Andersen,J.S., Ogg,S.C., Hay,R.T., Mann,M., and Lamond,A.I. (2006). Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics. Mol. Cell Proteomics 5, 2298-2310.

Vertegaal,A.C., Ogg,S.C., Jaffray,E., Rodriguez,M.S., Hay,R.T., Andersen,J.S., Mann,M., and Lamond,A.I. (2004). A proteomic study of SUMO-2 target proteins. J. Biol. Chem. 279, 33791-33798.

Partner

LUMC

Fellow

Zhenyu Xiao

Project

Maintaining genome stability by SUMO and Ub.