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Hepatoma-derived growth factor is a nuclear targeted mitogen containing a PWWP domain that mediates binding to DNA. To date, almost nothing is known about the molecular mechanisms of the functions of hepatoma-derived growth factor, its routes of secretion and internalization or post-translational modifications. | ỊFEBS Journal SUMOylation of the hepatoma-derived growth factor negatively influences its binding to chromatin Ketan Thakar1 Rainer Niedenthal2 Elwy Okaz1 Sebastian Franken3 Astrid Jakobs2 Shivangi Gupta1 S0rge Kelm1 and Frank Dietz1 1 Department of Biochemistry Centre for Biomolecular Interactions Bremen CBIB University of Bremen Germany 2 Department of Biochemistry Hannover Medical School Germany 3 Department of PhysiologicalChemistry Rheinische-Friedrich-Wilhelm University of Bonn Germany Keywords HDGF related protein HRP nuclear localization PWWP domain SUMOylation Correspondence F. Dietz Department of Biochemistry Centre for Biomolecular Interactions Bremen CBIB University of Bremen Leobener Strasse im NW2 28359 Bremen Germany Fax 49 421 218 2981 Tel 49 421 218 4324 E-mail fdietz@uni-bremen.de Received 16 May 2007 revised 7 December 2007 accepted 16 January 2008 doi 10.1111 j.1742-4658.2008.06303.x Hepatoma-derived growth factor is a nuclear targeted mitogen containing a PWWP domain that mediates binding to DNA. To date almost nothing is known about the molecular mechanisms of the functions of hepatoma-derived growth factor its routes of secretion and internalization or post-translational modifications. In the present study we show for the first time that hepatoma-derived growth factor is modified by the covalent attachment of small ubiquitin-related modifier 1 SUMO-1 a post-translational modification with regulatory functions for an increasing number of proteins. Using a basal SUMOylation system in Escherichia coli followed by a MALDI-TOF-MS based peptide analysis we identified the lysine residue SUMOylated located in the N-terminal part of the protein adjacent to the PWWP domain. Surprisingly this lysine residue is not part of the consensus motif described for SUMOylation. With a series of hepatoma-derived growth factor mutants we then confirmed that this unusual location is also used in mammalian cells and that SUMOylation of hepatoma-derived growth factor
