Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 21 June 2011
Vol. 4, Issue 178, p. rs4
[DOI: 10.1126/scisignal.2001484]

RESEARCH RESOURCES

Comparative Proteomic Analysis Identifies a Role for SUMO in Protein Quality Control

Michael H. Tatham1, Ivan Matic1,2, Matthias Mann2, and Ronald T. Hay1*

1 Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
2 Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.

Abstract: The small ubiquitin-like modifiers (SUMOs) alter the functions of diverse cellular proteins by covalent posttranslational modification and thus influence many cellular functions, including gene transcription, cell cycle, and DNA repair. Although conjugation by ubiquitin and SUMO-2/3 are largely functionally and mechanistically independent from one another, both appear to increase under conditions of proteasome inhibition. To better understand the relationship between SUMO and protein degradation by the proteasome, we performed a quantitative proteomic analysis of SUMO-2 substrates after short- and long-term inhibition of the proteasome with MG132. Comparisons with changes to the SUMO-2 conjugate subproteome in response to heat stress revealed qualitative and quantitative parallels between both conditions; however, in contrast to heat stress, the MG132-triggered increase in SUMO-2 conjugation depended strictly on protein synthesis, implying that the accumulation of newly synthesized, misfolded proteins destined for degradation by the proteasome triggered the SUMO conjugation response. Furthermore, proteasomal inhibition resulted in the accumulation of conjugated forms of all SUMO paralogs in insoluble protein inclusions and in the accumulation on SUMO-2 substrates of lysine-63–linked polyubiquitin chains, which are not thought to serve as signals for proteasome-mediated degradation. Together, these findings suggest multiple, proteasome-independent roles for SUMOs in the cellular response to the accumulation of misfolded proteins.

* To whom correspondence should be addressed. E-mail: r.t.hay{at}dundee.ac.uk

Citation: M. H. Tatham, I. Matic, M. Mann, R. T. Hay, Comparative Proteomic Analysis Identifies a Role for SUMO in Protein Quality Control. Sci. Signal. 4, rs4 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
RSUME Enhances Glucocorticoid Receptor SUMOylation and Transcriptional Activity.
J. Druker, A. C. Liberman, M. Antunica-Noguerol, J. Gerez, M. Paez-Pereda, T. Rein, J. A. Iniguez-Lluhi, F. Holsboer, and E. Arzt (2013)
Mol. Cell. Biol. 33, 2116-2127
   Abstract »    Full Text »    PDF »
Global Subcellular Characterization of Protein Degradation Using Quantitative Proteomics.
M. Larance, Y. Ahmad, K. J. Kirkwood, T. Ly, and A. I. Lamond (2013)
Mol. Cell. Proteomics 12, 638-650
   Abstract »    Full Text »    PDF »
Quantitative Proteomics Reveals Factors Regulating RNA Biology as Dynamic Targets of Stress-induced SUMOylation in Arabidopsis.
M. J. Miller, M. Scalf, T. C. Rytz, S. L. Hubler, L. M. Smith, and R. D. Vierstra (2013)
Mol. Cell. Proteomics 12, 449-463
   Abstract »    Full Text »    PDF »
A Novel SUMO1-specific Interacting Motif in Dipeptidyl Peptidase 9 (DPP9) That Is Important for Enzymatic Regulation.
E. Pilla, U. Moller, G. Sauer, F. Mattiroli, F. Melchior, and R. Geiss-Friedlander (2012)
J. Biol. Chem. 287, 44320-44329
   Abstract »    Full Text »    PDF »
In vivo localization and identification of SUMOylated proteins in the brain of His6-HA-SUMO1 knock-in mice.
M. Tirard, H.-H. Hsiao, M. Nikolov, H. Urlaub, F. Melchior, and N. Brose (2012)
PNAS 109, 21122-21127
   Abstract »    Full Text »    PDF »
RNF4-Dependent Hybrid SUMO-Ubiquitin Chains Are Signals for RAP80 and Thereby Mediate the Recruitment of BRCA1 to Sites of DNA Damage.
C. M. Guzzo, C. E. Berndsen, J. Zhu, V. Gupta, A. Datta, R. A. Greenberg, C. Wolberger, and M. J. Matunis (2012)
Science Signaling 5, ra88
   Abstract »    Full Text »    PDF »
Dynamic SUMOylation Is Linked to the Activity Cycles of Androgen Receptor in the Cell Nucleus.
M. Rytinki, S. Kaikkonen, P. Sutinen, V. Paakinaho, V. Rahkama, and J. J. Palvimo (2012)
Mol. Cell. Biol. 32, 4195-4205
   Abstract »    Full Text »    PDF »
The Expanding Universe of Ubiquitin and Ubiquitin-Like Modifiers.
R. D. Vierstra (2012)
Plant Physiology 160, 2-14
   Full Text »    PDF »
Post-translational modification of cardiac proteasomes: functional delineation enabled by proteomics.
S. B. Scruggs, N. C. Zong, D. Wang, E. Stefani, and P. Ping (2012)
Am J Physiol Heart Circ Physiol 303, H9-H18
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882