Cell Signaling Technology

Product Pathways - Protein Stability

USP18 (D4E7) Rabbit mAb #4813

Applications Reactivity Sensitivity MW (kDa) Isotype
W IP H Endogenous 34, 39 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

USP18 (D4E7) Rabbit mAb detects endogenous levels of total USP18 protein. The doublet band detected by western blot represents full length (39 kDa) and amino-terminal deleted derivative of USP18 (8).

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro45 of human USP18 protein.

Western Blotting

Western Blotting

Western blot analysis of extracts from THP-1 cells, untreated or LPS-treated (1 µg/ml, 24 hours), using USP18 (D4E7) Rabbit mAb.

Background

Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action. Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD and JAMM enzymes (1,2). USP18 (also known as UBP43) is a deubiquitinase best known for catalyzing the removal of ISG15, an interferon-regulated ubibiquitin-like protein, from conjugated proteins (3). Removal of ISG15 from target proteins by the USP18 peptidase maintains the critical cellular balance of ISG15-conjugated proteins important for normal development and brain function (4,5). Following induction by IFN or LPS (6), USP18 binds the INF receptor subunit IFNAR2 and inhibits signal transduction through the JAK-STAT pathway (7). USP18 regulation of IFN signaling inhibits IFN-mediated apoptosis and does not necessarily rely on USP18 peptidase activity (8). As the therapeutic use of recombinant IFN can lead to refractory IFN signaling and a less effective response, the combination of IFN treatment and regulation of USP18 expression may produce a more positive outcome (9).

  1. Nijman, S.M. et al. (2005) Cell 123, 773-86.
  2. Nalepa, G. et al. (2006) Nat Rev Drug Discov 5, 596-613.
  3. Malakhov, M.P. et al. (2002) J Biol Chem 277, 9976-81.
  4. Rempel, L.A. et al. (2007) Reprod Biol Endocrinol 5, 13.
  5. Ritchie, K.J. et al. (2002) Genes Dev 16, 2207-12.
  6. Malakhova, O. et al. (2002) J Biol Chem 277, 14703-11.
  7. Malakhova, O.A. et al. (2006) EMBO J 25, 2358-67.
  8. Potu, H. et al. (2010) Cancer Res 70, 655-65.
  9. Sarasin-Filipowicz, M. et al. (2009) Mol Cell Biol 29, 4841-51.

Application References

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Companion Products

For Research Use Only. Not For Use In Diagnostic Procedures.

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