USP8 Antibody Usage And Synthesis

Source

Rabbit

Reactivity

Human;Monkey

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. The deubiquitinating enzyme ubiquitin-specific protease 8 is a cysteine protease belonging to the USP/UBP subfamily. Research studies have shown that USP8 is an essential growth-regulated enzyme indespensible for cell proliferation and survival. Indeed, conditional knock-out of murine USP8 was shown to promote a dramatic loss in expression of receptor tyrosine kinases, including EGFR, ErbB3, and c-Met. In agreement with these findings, USP8 inactivation leads to enhanced ubiquitination of ligand-activated EGFR. Furthermore, phosphorylation of USP8 at Ser680 results in its binding of 14-3-3, catalytic inactivation, and reduced EGFR deubiquitination. It appears as though USP8, in conjunction with components of the ESCRT-0 complex, plays an integral role in the early endosomal sorting machinery that functions to protect EGFR from lysosomal degradation.

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] Naviglio, S. et al. (1998) EMBO J 17, 3241-50.
[4] Niendorf, S. et al. (2007) Mol Cell Biol 27, 5029-39.
[5] Alwan, H.A. and van Leeuwen, J.E. (2007) J Biol Chem 282, 1658-69.
[6] Mizuno, E. et al. (2005) Mol Biol Cell 16, 5163-74.
[7] Mizuno, E. et al. (2007) Exp Cell Res 313, 3624-34.
[8] Row, P.E. et al. (2006) J Biol Chem 281, 12618-24.
[9] Berlin, I. et al. (2010) J Biol Chem 285, 34909-21.