This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yamaguchi, T.
Right arrow Articles by Kuehn, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamaguchi, T.
Right arrow Articles by Kuehn, M. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2005, p. 5171-5182, Vol. 25, No. 12
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.12.5171-5182.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mutation of SENP1/SuPr-2 Reveals an Essential Role for Desumoylation in Mouse Development

Taihei Yamaguchi,1,{dagger} Prashant Sharma,1,§ Meropi Athanasiou,2,§ Amit Kumar,1 Satoru Yamada,1,§ and Michael R. Kuehn1*

Laboratory of Protein Dynamics and Signaling Basic Research Program, SAIC—Frederick, National Cancer Institute, NCI—Frederick, Frederick, Maryland 217022

Received 30 March 2004/ Returned for modification 10 May 2004/ Accepted 11 March 2005

The covalent modification of proteins by the small ubiquitin-like protein SUMO has been implicated in the regulation of numerous biological processes, including nucleocytoplasmic transport, genomic stability, and gene transcription. Sumoylation occurs by a multienzyme process similar to ubiquitination and, in Saccharomyces cerevisiae, is reversed by desumoylating enzymes encoded by the Ulp1 and Smt4/Ulp2 genes. The physiological importance of desumoylation has been revealed by mutations in either gene, which lead to nonoverlapping defects in cell cycle transition and meiosis. Several mammalian Ulp homologues have been identified, but, to date, nothing is known of the phenotypic effects of their loss of function. Here, we describe a random retroviral insertional mutation of one homolog, mouse SENP1/SuPr-2. The mutation causes increased steady-state levels of the sumoylated forms of a number of proteins and results in placental abnormalities incompatible with embryonic development. Our findings provide the first insight into the critical importance of regulating sumoylation in mammals.


* Corresponding author. Mailing address: Laboratory of Protein Dynamics and Signaling, NCI-Frederick, Bldg. 560, Rm. 12-90, Frederick, MD 21702. Phone: (301) 846-7451. Fax: (301) 846-1666. E-mail: mkuehn{at}mail.nih.gov.

{dagger} Present address: Kagoshima University Dental School, Department of Preventive Dentistry, Sakuragaoka 8-35-1, Kagoshima-shi, Kagoshima 890-8544, Japan.

{ddagger} Present address: Osaka University Graduate School of Dentistry, Department of Periodontology, Division of Oral Biology and Disease Control, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.

§ P.S. and M.A. contributed equally to this work.


Molecular and Cellular Biology, June 2005, p. 5171-5182, Vol. 25, No. 12
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.12.5171-5182.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Yeh, E. T. H. (2009). SUMOylation and De-SUMOylation: Wrestling with Life's Processes. J. Biol. Chem. 284: 8223-8227 [Abstract] [Full Text]  
  • Kaikkonen, S., Jaaskelainen, T., Karvonen, U., Rytinki, M. M., Makkonen, H., Gioeli, D., Paschal, B. M., Palvimo, J. J. (2009). SUMO-Specific Protease 1 (SENP1) Reverses the Hormone-Augmented SUMOylation of Androgen Receptor and Modulates Gene Responses in Prostate Cancer Cells. Mol. Endocrinol. 23: 292-307 [Abstract] [Full Text]  
  • Evdokimov, E., Sharma, P., Lockett, S. J., Lualdi, M., Kuehn, M. R. (2008). Loss of SUMO1 in mice affects RanGAP1 localization and formation of PML nuclear bodies, but is not lethal as it can be compensated by SUMO2 or SUMO3. J. Cell Sci. 121: 4106-4113 [Abstract] [Full Text]  
  • Brown, P. W., Hwang, K., Schlegel, P. N., Morris, P. L. (2008). Small ubiquitin-related modifier (SUMO)-1, SUMO-2/3 and SUMOylation are involved with centromeric heterochromatin of chromosomes 9 and 1 and proteins of the synaptonemal complex during meiosis in men. Hum Reprod 23: 2850-2857 [Abstract] [Full Text]  
  • Lima, C. D., Reverter, D. (2008). Structure of the Human SENP7 Catalytic Domain and Poly-SUMO Deconjugation Activities for SENP6 and SENP7. J. Biol. Chem. 283: 32045-32055 [Abstract] [Full Text]  
  • Zhang, F.-P., Mikkonen, L., Toppari, J., Palvimo, J. J., Thesleff, I., Janne, O. A. (2008). Sumo-1 Function Is Dispensable in Normal Mouse Development. Mol. Cell. Biol. 28: 5381-5390 [Abstract] [Full Text]  
  • Bawa-Khalfe, T., Cheng, J., Wang, Z., Yeh, E. T. H. (2007). Induction of the SUMO-specific Protease 1 Transcription by the Androgen Receptor in Prostate Cancer Cells. J. Biol. Chem. 282: 37341-37349 [Abstract] [Full Text]  
  • Tillmanns, S., Otto, C., Jaffray, E., Du Roure, C., Bakri, Y., Vanhille, L., Sarrazin, S., Hay, R. T., Sieweke, M. H. (2007). SUMO Modification Regulates MafB-Driven Macrophage Differentiation by Enabling Myb-Dependent Transcriptional Repression. Mol. Cell. Biol. 27: 5554-5564 [Abstract] [Full Text]  
  • Deyrieux, A. F., Rosas-Acosta, G., Ozbun, M. A., Wilson, V. G. (2007). Sumoylation dynamics during keratinocyte differentiation. J. Cell Sci. 120: 125-136 [Abstract] [Full Text]  
  • Nowak, M., Hammerschmidt, M. (2006). Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development. Mol. Biol. Cell 17: 5324-5336 [Abstract] [Full Text]  
  • Colby, T., Matthai, A., Boeckelmann, A., Stuible, H.-P. (2006). SUMO-Conjugating and SUMO-Deconjugating Enzymes from Arabidopsis. Plant Physiol. 142: 318-332 [Abstract] [Full Text]  
  • Di Bacco, A., Ouyang, J., Lee, H.-Y., Catic, A., Ploegh, H., Gill, G. (2006). The SUMO-Specific Protease SENP5 Is Required for Cell Division. Mol. Cell. Biol. 26: 4489-4498 [Abstract] [Full Text]