This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Di Bacco, A. Articles by Gill, G. Search for Related Content PubMed PubMed Citation Articles by Di Bacco, A. Articles by Gill, G.

The SUMO-Specific Protease SENP5 Is Required for Cell Division

Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115,¹ Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142²

Received 1 December 2005/ Returned for modification 11 January 2006/ Accepted 28 March 2006

Posttranslational modification of substrates by the small ubiquitin-like modifier, SUMO, regulates diverse biological processes, including transcription, DNA repair, nucleocytoplasmic trafficking, and chromosome segregation. SUMOylation is reversible, and several mammalian homologs of the yeast SUMO-specific protease Ulp1, termed SENPs, have been identified. We demonstrate here that SENP5, a previously uncharacterized Ulp1 homolog, has SUMO C-terminal hydrolase and SUMO isopeptidase activities. In contrast to other SENPs, the C-terminal catalytic domain of SENP5 preferentially processed SUMO-3 compared to SUMO-1 precursors and preferentially removed SUMO-2 and SUMO-3 from SUMO-modified RanGAP1 in vitro. In cotransfection assays, SENP5 preferentially reduced high-molecular-weight conjugates of SUMO-2 compared to SUMO-1 in vivo. Full-length SENP5 localized to the nucleolus. Deletion of the noncatalytic N-terminal domain led to loss of nucleolar localization and increased de-SUMOylation activity in vivo. Knockdown of SENP5 by RNA interference resulted in increased levels of SUMO-1 and SUMO-2/3 conjugates, inhibition of cell proliferation, defects in nuclear morphology, and appearance of binucleate cells, revealing an essential role for SENP5 in mitosis and/or cytokinesis. These findings establish SENP5 as a SUMO-specific protease required for cell division and suggest that mechanisms involving both the catalytic and noncatalytic domains determine the distinct substrate specificities of the mammalian SUMO-specific proteases.

This article has been cited by other articles:

• Fang, S.-C., Umen, J. G. (2008). A Suppressor Screen in Chlamydomonas Identifies Novel Components of the Retinoblastoma Tumor Suppressor Pathway. Genetics 178: 1295-1310 [Abstract] [Full Text]  
• Vethantham, V., Rao, N., Manley, J. L. (2007). Sumoylation Modulates the Assembly and Activity of the Pre-mRNA 3' Processing Complex. Mol. Cell. Biol. 27: 8848-8858 [Abstract] [Full Text]  
• Mikolajczyk, J., Drag, M., Bekes, M., Cao, J. T., Ronai, Z., Salvesen, G. S. (2007). Small Ubiquitin-related Modifier (SUMO)-specific Proteases: PROFILING THE SPECIFICITIES AND ACTIVITIES OF HUMAN SENPs. J. Biol. Chem. 282: 26217-26224 [Abstract] [Full Text]  
• Griffith, M. E., Mayer, U., Capron, A., Ngo, Q. A., Surendrarao, A., McClinton, R., Jurgens, G., Sundaresan, V. (2007). The TORMOZ Gene Encodes a Nucleolar Protein Required for Regulated Division Planes and Embryo Development in Arabidopsis. Plant Cell 19: 2246-2263 [Abstract] [Full Text]  
• Herrmann, J., Lerman, L. O., Lerman, A. (2007). Ubiquitin and Ubiquitin-Like Proteins in Protein Regulation. Circ. Res. 100: 1276-1291 [Abstract] [Full Text]  
• Zunino, R., Schauss, A., Rippstein, P., Andrade-Navarro, M., McBride, H. M. (2007). The SUMO protease SENP5 is required to maintain mitochondrial morphology and function. J. Cell Sci. 120: 1178-1188 [Abstract] [Full Text]