USP18 (D4E7) Rabbit mAb Usage And Synthesis

Source

Rabbit

Reactivity

Human

Background

Ubiquitinating enzymes catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme action. Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD, and JAMM enzymes. USP18 is a deubiquitinase best known for catalyzing the removal of ISG15, an interferon-regulated ubiquitin-like protein, from conjugated proteins. 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. Following induction by IFN or LPS, USP18 binds the INF receptor subunit IFNAR2 and inhibits signal transduction through the Jak/Stat pathway. USP18 regulation of IFN signaling inhibits IFN-mediated apoptosis and does not necessarily rely on USP18 peptidase activity. 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.

References

[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, 2358-2367.
[8] Potu, H. et al. (2010) Cancer Res 70, 655-65.
[9] Sarasin-Filipowicz, M. et al. (2009) Mol Cell Biol 29, 4841-51.

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