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Ubiquitin & UBL Signaling








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UBL Signaling Catalog

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Browse hundreds of high-quality research products, including proteins and antibodies, for activating enzymes (E1s), conjugating enzymes (E2s), ligases (E3s) and deconjugating enzymes (DCEs), plus an innovative range of ubiquitin-, SUMO-, NEDD8-, ISG15- and FAT10-associated proteins and derivatives. Discover ubiquitin- and Ubl-reactive antibodies, kits for the study of ubiquitin, SUMO, and NEDD8 conjugation, and our easy-to-use UbiQaptureTM and SUMO-QaptureTM kits for the detection and isolation of ubiquitinylated and SUMOylated proteins.

 

Ubiquitin

Ubiquitinylation of cellular proteins is a highly complex and tightly regulated process that targets, in a specific manner, thousands of cellular proteins. It is carried out by a modular cascade of enzymes with high specificity towards target proteins. Conjugation of ubiquitin can serve a variety of non-proteolytic functions, including activation of enzymes, modulation of membrane dynamics, or routing of the tagged proteins to their sub-cellular destination (Figure 1).

Figure 1. Differing ubiquitin modification resulting in distinct functions.
 

Ubiquitin-like Proteins

There are at least 10 conjugatable ‘cousins’ of ubiquitin including, amongst others, SUMO, NEDD8, ISG15 and FAT10. These ubiquitin-like proteins (Ubls) can be covalently attached to target proteins for a variety of signalling processes in the cell and may function as critical regulators of many cellular processes, including transcription, DNA repair, signal transduction, autophagy, and cell-cycle control. There is a growing body of data implicating the dysregulation of Ubl-substrate modification and mutations in the Ubl-conjugation machinery in the etiology and progression of a number of human diseases.

 

Ubl Cascade Enzymes (E1s, E2s and E3s)

The complexity of the ubiquitin and ubiquitin-like protein cascades is considerable. In mammals, there are some ten activating enzymes (E1s) known, some twenty plus conjugating enzymes (E2s), over eight hundred ligases (E3s), and approaching one hundred deconjugating enzymes. These varied components work in a hierarchical context and, for appropriate modification with ubiquitin or a Ubl to occur, the correct combination of E1, E2, E3, substrate, and deconjugating enzyme must all work in concert. The cascades for the ubiquitin-like proteins appear not to be as complex as that of ubiquitin with a reduced number of component possibilities.

 

Deconjugating Enzymes (DCEs)

Deconjugating enzymes (DCEs) can hydrolyse a peptide, amide, ester or thioester bond at the C-terminus of ubiquitin, including the post translationally formed isopeptide bonds found in mono-, multi-, and polyubiquitinylated conjugates. DCEs thus have the potential to regulate any ubiquitin/Ubl-mediated cellular process. Their conservation and widespread occurrence in eukaryotes, prokaryotes and viruses shows that these proteases constitute an essential class of enzymes.

 

UbiQapture®-Q kit

Market-leading tool for isolation and detection of ubiquitinylated proteins.

For isolation and enrichment of ubiquitinylated proteins. The UbiQapture®-Q Kit is an efficient tool for the selective isolation of ubiquitinylated proteins. The Kit facilitates the isolation of both mono- and poly-ubiquitinylated proteins (independent of lysine residue chain linkage) from cell extracts, tissue lysates and in vitro assay solutions through use of a high-binding affinity matrix.

Applications:

  1. Isolation and detection of the full range of ubiquitinylated protein conjugates (mono-/multi-/poly-ubiquitin modified, lysine linkage independent) from specific cell/tissue lysates of interest.
  2. Capture and analysis of specific ubiquitinylated protein conjugates of interest from particular cell/tissue lysates.
  3. Purification/pull down of ubiquitinylated proteins from cell free in vitro assays
  4. Release of free proteins in their active/native form by cleavage of ubiquitin/ubiquitin chains from the UbiQapture®-Q matrix using deubiquitinylating enzymes.
  5. Release of ubiquitinylated proteins in their active/native form by elution from the UbiQapture®-Q matrix.

 

Literature References

  • The complete amino acid sequence of ubiquitin, an adenylate cyclase stimulating polypeptide probably universal in living cells: D.H. Schlesinger, et al.; Biochemistry 14, 2214 (1975)
  • Ubiquitin superfolds: intrinsic and attachable regulators of cellular activities?: R.J. Mayer, et al.; Fold. Des. 3, R97 (1998)
  • Ubiquitin and ubiquitin-like proteins as multifunctional signals: R.L. Welchman, et al.; Nat. Rev. Mol. Cell Biol. 6, 599 (2005)
  • Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry: D. Meierhofer, et al.; J. Proteome Res. 7, 4566 (2008)
  • Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages: H.T. Kim, et al.; J. Biol. Chem. 282, 17375 (2007)
  • A ubiquitin ligase complex assembles linear polyubiquitin chains: T. Kirisako, et al.; EMBO J. 25, 4877 (2006)
  • Ubiquitylation on canonical and non-canonical sites targets the transcription factor neurogenin for ubiquitin-mediated proteolysis: J.M. Vosper, et al.; J. Biol. Chem. 284, 15458 (2009)
  • The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction: M.H. Glickman & A. Ciechanover; Physiol. Rev. 82, 373 (2002)
  • Modification of proteins by ubiquitin and ubiquitin-like proteins:O. Kerscher, et al.; Annu. Rev. Cell Dev. Biol. 22, 159 (2006)
  • Innate link between NF-kappaB activity and ubiquitin-like modifiers: V. Lang and M.S. Rodriguez; Biochem. Soc. Trans. 36, 853 (2008)
  • A role for ubiquitin in selective autophagy: V. Kirkin, et al.; Mol. Cell 34, 259 (2009)
  • Mechanism and function of deubiquitinating enzymes: A.Y. Amerik & M. Hochstrasser; Biochim. Biophys. Acta 1695, 189 (2004)

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