Enabling Protein Degradation Drug Discovery

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  • Name
    Catalogue Number
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  • Name:
    USP6 CD(529-1406) [GST-tagged]
    Catalogue Number:
    50 µg
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  • Species
  • Source
    Insect (Sf21)
  • Quantity
    50 µg
  • Storage
  • Concentration
    0.5 mg/ml
  • Formulation
    50 mM HEPES pH 7.5, 150 mM sodium chloride, 2 mM dithiothreitol, 10% glycerol
  • Molecular Weight
  • Stability
    12 months at -70°C; aliquot as required
  • Protein Sequence
    Accession number: NP_004496. For full protein sequence information download the Certificate of Analysis pdf.
  • QA; Protein Identification
    Confirmed by mass spectrometry.
  • QA; Activity
    Deubiquitylase Enzyme Assay: The activity of GST-USP6 CD(529-1406) was validated by determining the increase in fluorescence measured as a result of the enzyme catalysed cleavage of the fluorogenic substrate Ubiquitin-Rhodamine110-Glycine generating Ubiquitin and Rhodamine110-Glycine. Incubation of the substrate in the presence or absence of GST-USP6 CD(529-1406) was compared confirming the deubiquitylating activity of GST-USP6 CD(529-1406).
Deconjugating enzymes (DCEs) are proteases that process ubiquitin or ubiquitin-like gene products, reverse the modification of proteins by a single ubiquitin or ubiquitin-like protein (UBL) and remodel polyubiquitin (or poly-UBL) chains on target proteins (Reyes-Turcu et al., 2009). The deubiquitylating – or deubiquitinating – enzymes (DUBs) represent the largest family of DCEs and regulate ubiquitin dependent signalling pathways. The activities of the DUBs include the generation of free ubiquitin from precursor molecules, the recycling of ubiquitin following substrate degradation to maintain cellular ubiquitin homeostasis and the removal of ubiquitin or ubiquitin-like proteins (UBL) modifications through chain editing to rescue proteins from proteasomal degradation or to influence cell signalling events (Komander et al., 2009). There are two main classes of DUB, cysteine proteases and metalloproteases. Ubiquitin specific protease 6 (USP6) is a member of the cysteine protease enzyme family and cloning of the gene was first described by Nakamura et al. (1992). USP6 was the first DUB to be identified as an oncogene (Oliveira and Chou, 2012). Multiple DUBs, including A20, CYLD, Cezanne, USP21 and USP15, have been shown to function as negative regulators of NFκB; however, only one DUB, USP6, induces NFκB activation (Pringle et al., 2012). USP6 is translocated and overexpressed in aneurysmal bone cyst (ABC), a paediatric tumour characterized by extensive bone degradation and inflammatory recruitment (Pringle et al., 2012). Recent work has shown that USP6 is part of a signalling pathway that contributes to ABC pathogenesis, raising the possibility that development of USP-specific inhibitors or NF-κB antagonists might be effective novel strategies for the treatment of these tumours (Ye et al., 2010).
Komander D, Clague MJ and Urbe S (2009) Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol, 10, 550-563.
Nakamura T, Hillova J, Mariage-Samson R, Onno M, Huebner K, Cannizzaro LA, et al. (1992) A novel transcriptional unit of the tre oncogene widely expressed in human cancer cells. Oncogene, 7, 733-741.
Oliveira AM and Chou MM (2012) The TRE17/USP6 oncogene: a riddle wrapped in a mystery inside an enigma. Front Biosci (Schol Ed), 4, 321-334.
Pringle LM, Young R, Quick L, Riquelme DN, Oliveira AM, May MJ, et al. (2012) Atypical mechanism of NF-kappaB activation by TRE17/ubiquitin-specific protease 6 (USP6) oncogene and its requirement in tumorigenesis. Oncogene, 31, 3525-3535.
Reyes-Turcu FE, Ventii KH and Wilkinson KD (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annual review of biochemistry, 78, 363-397.
Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, et al. (2010) TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene, 29, 3619-3629.