Enabling Protein Degradation Drug Discovery

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  • Name
    Catalogue Number
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  • Name:
    MuRF1 [untagged]
    Catalogue Number:
    25 µg
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  • Species
  • Source
  • Quantity
    25 µg
  • Storage
  • Concentration
  • Formulation
    50mM sodium Bicarbonate pH10, 250mM NaCl, 0.03% Brij35, 0.5mMTCEP
  • Molecular Weight
  • Stability
    12 months at -70°C; aliquot as required
  • Protein Sequence
    Accession number: NP_115977.2 For full protein sequence information download the Certificate of Analysis pdf.
  • QA; Protein Identification
    Confirmed by mass spectrometry.
  • QA; Activity
    E3 Ligase Assay: The ubiquitin conjugating activity of MuRF1 was validated through its ability to catalyse the generation of polyubiquitin chains in the presence of the E1 activating enzyme His-UBE1, the E2 conjugating enzyme His-UBE2D3 (UbcH5c) (several E2s were tested, data generated with this E2 is provided by way of example) and ubiquitin. Incubation of MuRF1 for 60 minutes at 30oC in the presence of ubiquitin, His-UBE1, His-UBE2D3 and ATP (Lane 1) was compared alongside two control reactions with either ATP (Lane 2) or MuRF1 (Lane 3) excluded from the reaction. Ubiquitin conjugates were identified by Western blotting using an anti-ubiquitin conjugate antibody and these were observed only in the presence of both ATP and MuRF1.

The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the regulated and targeted proteasome-dependent degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). Muscle Ring Finger protein 1 (MuRF1) is a member of the E3 protein ligase family and cloning of the human gene was first described by Dai and Liew et al. (2001). Muscle atrophy is a pathological condition associated with a number of diseases including cancer, metabolic disorders and AIDS. The associated up-regulation of MuRF1 and increased muscle protein turnover observed in disease models highlights the potential value of targeting this E3 ligase in order to address muscle wasting conditions. Atrophy of skeletal muscle can occur through lack of use and denervation associated with disease states such as cancer cachexia, cardiac failure and other muscle wasting conditions in humans (Cohen et al., 2009; Rottbauer et al., 2006; Seidman et al., 2001; Poetter et al., 1996). Myosin Light Chain 1 (MyLC1) and MyLC2 are required for thick-filament stabilization and normal contractility in the myofibrils of skeletal muscle. Loss of function mutations in these proteins results in a perturbation of contractility and a striking disorganization of the thick filaments which leads to muscle wasting conditions (Cohen et al., 2009; Seidman et al., 2001). Rapid loss in muscle mass due to protein degradation of the myofibrilar components is mediated by the ubiquitin proteasome pathway. During this process there is a marked increase in MuRF1 concentration which is thought to act directly on specific components of the myofibril to promote its disassembly and degradation during atrophy (Cohen et al., 2009). Mice lacking the RING domain of MuRF1 show significantly reduced loss of muscle mass following denervation highlighting the therapeutic importance of this target in muscle wasting disease (Cohen et al., 2009).

Cohen S, Brault JJ, Gygi SP, Glass DJ, Valenzuela DM, Gartner C, Latres E, Goldberg AL. (2009) During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol. 185, 1083-95.

Dai KS, Liew CC. (2001) A novel human striated muscle RING zinc finger protein, SMRZ, interacts with SMT3b via its RING domain. J. Biol. Chem. 276, 23992-23999.

Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND. (1996) Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet. 13, 63-9.

Rottbauer W, Wessels G, Dahme T, Just S, Trano N, Hassel D, Burns C, Katus H, Fishman M. (2006) Cardiac myosin light chain-2: a novel essential component of thick-myofilament assembly and contractility of the heart. Circ.Res. 99, 323–331.

Seidman JG, Seidman C. (2001) The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms.
Cell 104, 557-67.