SUMO enzymes

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SUMO enzymatic cascade SUMOpathway2.jpg
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]

Catalysis chemical process

Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst, which is not consumed in the catalyzed reaction and can continue to act repeatedly. Because of this, only very small amounts of catalyst are required to alter the reaction rate in principle.

SUMO protein

Small Ubiquitin-like Modifier proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle.

Ubiquitin

Ubiquitin is a small regulatory protein found in most tissues of eukaryotic organisms, i.e. it occurs ubiquitously. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the 1970s and 1980s. Four genes in the human genome code for ubiquitin: UBB, UBC, UBA52 and RPS27A.

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 The set of life-sustaining chemical transformations within the cells of organisms

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of food to energy to run cellular processes; the conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of nitrogenous wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments..

Metabolic network

A metabolic network is the complete set of metabolic and physical processes that determine the physiological and biochemical properties of a cell. As such, these networks comprise the chemical reactions of metabolism, the metabolic pathways, as well as the regulatory interactions that guide these reactions.

Metabolic network modelling

Metabolic network reconstruction and simulation allows for an in-depth insight into the molecular mechanisms of a particular organism. In particular, these models correlate the genome with molecular physiology. A reconstruction breaks down metabolic pathways into their respective reactions and enzymes, and analyzes them within the perspective of the entire network. In simplified terms, a reconstruction collects all of the relevant metabolic information of an organism and compiles it in a mathematical model. Validation and analysis of reconstructions can allow identification of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. This knowledge can then be applied to create novel biotechnology.

Related Research Articles

Deubiquitinating enzyme

Deubiquitinating enzymes (DUBs), also known as deubiquitinating peptidases, deubiquitinating isopeptidases, deubiquitinases, ubiquitin proteases, ubiquitin hydrolases, ubiquitin isopeptidases, are a large group of proteases that cleave ubiquitin from proteins and other molecules. Ubiquitin is attached to proteins in order to regulate the degradation of proteins via the proteasome and lysosome; coordinate the cellular localisation of proteins; activate and inactivate proteins; and modulate protein-protein interactions. DUBs can reverse these effects by cleaving the peptide or isopeptide bond between ubiquitin and its substrate protein. In humans there are nearly 100 DUB genes, which can be classified into two main classes: cysteine proteases and metalloproteases. The cysteine proteases comprise ubiquitin-specific proteases (USPs), ubiquitin C-terminal hydrolases (UCHs), Machado-Josephin domain proteases (MJDs) and ovarian tumour proteases (OTU). The metalloprotease group contains only the Jab1/Mov34/Mpr1 Pad1 N-terminal+ (MPN+) (JAMM) domain proteases.

Abgent is a global biotechnology company based in San Diego, California, US with offices in Maidenhead, UK and Suzhou, China and distributors around the world. Abgent develops antibodies and related agents to study proteins involved in cellular function and disease. Abgent's antibodies target key areas of research including autophagy, neuroscience, cancer, stem cells and more. Abgent was acquired in 2011 by WuXi AppTec, a global pharmaceutical, biopharmaceutical, and medical device outsourcing company with operations in China and the United States.

UBE2I protein-coding gene in the species Homo sapiens

SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the UBE2I gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe its function.

PIAS4 protein-coding gene in the species Homo sapiens

E3 SUMO-protein ligase PIAS4 is one of several protein inhibitor of activated STAT (PIAS) proteins. It is also known as protein inhibitor of activated STAT protein gamma, and is an enzyme that in humans is encoded by the PIAS4 gene.

PIAS1 protein-coding gene in the species Homo sapiens

E3 SUMO-protein ligase PIAS1 is an enzyme that in humans is encoded by the PIAS1 gene.

Protein inhibitor of activated STAT2 protein-coding gene in the species Homo sapiens

E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the PIAS2 gene.

RANGAP1 protein-coding gene in the species Homo sapiens

Ran GTPase-activating protein 1 is an enzyme that in humans is encoded by the RANGAP1 gene.

UBE2N protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 N is a protein that in humans is encoded by the UBE2N gene.

CKS1B protein-coding gene in the species Homo sapiens

Cyclin-dependent kinases regulatory subunit 1 is a protein that in humans is encoded by the CKS1B gene.

SAE1 protein-coding gene in the species Homo sapiens

SUMO-activating enzyme subunit 1 is a protein that in humans is encoded by the SAE1 gene.

UBE2E3 protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 E3 is a protein that in humans is encoded by the UBE2E3 gene.

SENP2 protein-coding gene in the species Homo sapiens

Sentrin-specific protease 2 is an enzyme that in humans is encoded by the SENP2 gene.

SENP8 protein-coding gene in the species Homo sapiens

Sentrin-specific protease 8 is an enzyme that in humans is encoded by the SENP8 gene.

Cullin

Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form Cullin-RING ubiquitin ligases (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination.

ATG8 protein-coding gene in the species Saccharomyces cerevisiae S288c

Autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. The transient conjugation of Atg8 to the autophagosomal membrane through a ubiquitin-like conjugation system is essential for autophagy in eukaryotes. Even though there are homologues in animals, this article mainly focuses on its role in lower eukaryotes such as Saccharomyces cerevisiae.

APC/C activator protein CDH1

Cdh1 is one of the substrate adaptor protein of the anaphase-promoting complex (APC) in the budding yeast Saccharomyces cerevisiae. Functioning as an activator of the APC/C, Cdh1 regulates the activity and substrate specificity of this ubiquitin E3-ligase.

UBA2 protein-coding gene in the species Homo sapiens

Ubiquitin-like 1-activating enzyme E1B (UBLE1B) also known as SUMO-activating enzyme subunit 2 (SAE2) is an enzyme that in humans is encoded by the UBA2 gene.

Ubiquitin-like protein InterPro Domain

Ubiquitin-like proteins (UBLs) are a family of small proteins involved in post-translational modification of other proteins in a cell, usually with a regulatory function. The UBL protein family derives its name from the first member of the class to be discovered, ubiquitin (Ub), best known for its role in regulating protein degradation through covalent modification of other proteins. Following the discovery of ubiquitin, many additional evolutionarily related members of the group were described, involving parallel regulatory processes and similar chemistry. UBLs are involved in a widely varying array of cellular functions including autophagy, protein trafficking, inflammation and immune responses, transcription, DNA repair, RNA splicing, and cellular differentiation.

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
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