SUMOylation of the hepatoma-derived growth factor negatively influences its binding to chromatin.
Article Details
- CitationCopy to clipboard
Thakar K, Niedenthal R, Okaz E, Franken S, Jakobs A, Gupta S, Kelm S, Dietz F
SUMOylation of the hepatoma-derived growth factor negatively influences its binding to chromatin.
FEBS J. 2008 Apr;275(7):1411-26. doi: 10.1111/j.1742-4658.2008.06303.x. Epub 2008 Mar 5.
- PubMed ID
- 18331345 [ View in PubMed]
- Abstract
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 takes place in the nucleus. Finally, we demonstrate that SUMOylated hepatoma-derived growth factor is not binding to chromatin, in contrast to its unSUMOylated form. These observations potentially provide new perspectives for a better understanding of the functions of hepatoma-derived growth factor.