SUMO enzymes

SUMO enzymatic cascade

SUMO enzymatic cascade catalyzes the dynamic posttranslational modification process of sumoylation (i.e. transfer of SUMO protein to other proteins). The Small Ubiquitin-related Modifier, SUMO-1,^[1][2] is a ubiquitin-like family member that is conjugated to its substrates through three discrete enzymatic steps (see the figure on the right): activation, involving the E1 enzyme (SAE1/SAE2);^[3] conjugation, involving the E2 enzyme (UBE2I);^[4][5] substrate modification, through the cooperation of the E2 and E3^[6] protein ligases.^[7]

SUMO pathway modifies hundreds of proteins that participate in diverse cellular processes.^[8] SUMO pathway is the most studied ubiquitin-like pathway that regulates a wide range of cellular events,^[9] evidenced by a large number of sumoylated proteins identified in more than ten large-scale studies.^{[10][11][12][13][14][15][16][17][18][19][20]}

See also

• Metabolism
• Metabolic network
• Metabolic network modelling

References

1. Johnson, E.S. Protein modification by SUMO. Annu. Rev. Biochem. 73, 355–382 (2004)
2. Melchior, F. SUMO–nonclassical ubiquitin. Annu. Rev. Cell Dev. Biol. 16, 591–626 (2000)
3. Boggio R et al., A mechanism for inhibiting the SUMO pathway. Mol Cell. 2004 Nov 19;16(4):549-61
4. Bernier-Villamor, V. , Sampson, D.A. , Matunis, M.J. & Lima, C.D. Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108, 345–356
5. Lin, D. et al. Identification of a substrate recognition site on Ubc9. J. Biol. Chem. 277, 21740–21748 (2002)
6. Reverter, D. & Lima, C.D. Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435, 687–692
7. Melchior, F. , Schergaut, M. & Pichler, A. SUMO: ligases, isopeptidases and nuclear pores. Trends Biochem. Sci. 28, 612–618
8. Johnson ES. Protein modification by SUMO. Annu Rev Biochem 2004;73:355–82
9. O. Kerscher, R. Felberbaum and M. Hochstrasser, Modification of proteins by ubiquitin and ubiquitin-like proteins, Annu. Rev. Cell Dev. Biol. (2006) Jun 5, Electronic publication ahead of print
10. W. Zhou, J.J. Ryan and H. Zhou, Global analyses of sumoylated proteins in Saccharomyces cerevisiae. Induction of protein sumoylation by cellular stresses, J. Biol. Chem. 279 (2004), pp. 32262–32268
11. T. Li, E. Evdokimov, R.F. Shen, C.C. Chao, E. Tekle, T. Wang, E.R. Stadtman, D.C. Yang and P.B. Chock, Sumoylation of heterogeneous nuclear ribonucleoproteins, zinc finger proteins, and nuclear pore complex proteins: a proteomic analysis, Proc. Natl. Acad. Sci. U. S. A. 101 (2004), pp. 8551–8556
12. J.A. Wohlschlegel, E.S. Johnson, S.I. Reed and J.R. Yates, 3rd, Global analysis of protein sumoylation in Saccharomyces cerevisiae, J. Biol. Chem. (2004)
13. V.G. Panse, U. Hardeland, T. Werner, B. Kuster and E. Hurt, A proteome-wide approach identifies sumoylated substrate proteins in yeast, J. Biol. Chem. (2004)
14. A.C. Vertegaal, S.C. Ogg, E. Jaffray, M.S. Rodriguez, R.T. Hay, J.S. Andersen, M. Mann and A.I. Lamond, A proteomic study of SUMO-2 target proteins, J. Biol. Chem. 279 (2004), pp. 33791–33798
15. [72] C. Denison, A.D. Rudner, S.A. Gerber, C.E. Bakalarski, D. Moazed and S.P. Gygi, A proteomic strategy for gaining insights into protein sumoylation in yeast, Mol. Cell. Proteomics 4 (2005), pp. 246–254
16. J.T. Hannich, A. Lewis, M.B. Kroetz, S.J. Li, H. Heide, A. Emili and M. Hochstrasser, Defining the SUMO-modified proteome by multiple approaches in Saccharomyces cerevisiae, J. Biol. Chem. 280 (2005), pp. 4102–4110
17. Y. Zhao, S.W. Kwon, A. Anselmo, K. Kaur and M.A. White, Broad spectrum identification of cellular small ubiquitin-related modifier (SUMO) substrate proteins, J. Biol. Chem. 279 (2004), pp. 20999–21002
18. L.L. Manza, S.G. Codreanu, S.L. Stamer, D.L. Smith, K.S. Wells, R.L. Roberts and D.C. Liebler, Global shifts in protein sumoylation in response to electrophile and oxidative stress, Chem. Res. Toxicol. 17 (2004), pp. 1706–1715
19. T. Li, R. Santockyte, R.F. Shen, E. Tekle, G. Wang, D.C. Yang and P.B. Chock, A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers, Arch. Biochem. Biophys. 453 (2006), pp. 70–74
20. G. Rosas-Acosta, W.K. Russell, A. Deyrieux, D.H. Russell and V.G. Wilson, A universal strategy for proteomic studies of SUMO and other ubiquitin-like modifiers, Mol. Cell. Proteomics 4 (2005), pp. 56–72