COPS5 Antibody Usage And Synthesis

Source

Rabbit

Reactivity

Human;Mouse;Rat;Monkey

Background

The COP9 Signalosome is a ubiquitously expressed multiprotein complex that is involved in a vast array of cellular and developmental processes, which is thought to be attributed to its control over the ubiquitin-proteasome pathway. Typically, the CSN is composed of eight highly conserved subunits, each of which is homologous to one of the eight subunits that form the lid of the 26S proteasome particle, suggesting that these complexes have a common evolutionary ancestor. CSN was first identified in Arabidopsis thaliana mutants with a light-grown seedling phenotype when grown in the dark. The subsequent cloning of the constitutive morphogenesis 9 mutant from Arabidopsis thaliana was soon followed by the biochemical purification of the COP9-containing multiprotein complex. It is now widely accepted that the CSN directly interacts with cullin-RING ligase families of ubiquitin E3 complexes, and that CSN is required for their proper function. In addition, CSN may also regulate protein homeostasis through its association with protein kinases and deubiquitinating enzymes. Collectively, these activities position the CSN as a pivotal regulator of the DNA-damage response, cell-cycle control, and gene expression.COPS5/CSN5/Jab1 was originally identified as a transcriptional coactivator of c-Jun and subsequently discovered to be a fifth component and integral part of the CSN. As the catalytic center of the CSN, COPS5 is able to integrate multiple functions of the CSN complex such as cell-cycle control, transcription, and DNA-damage response by regulating the activity of CRLs through deneddylation of cullins. Indeed, COPS5 harbors a Mpr1-Pad1-N-terminal domain with an embedded Jab1/CSN5 MPN domain metalloenzyme motif that is essential for the CSN isopeptidase activity responsible for deneddylation of CRLs. COPS5 is an evolutionarily conserved 38 kDa protein in humans, mice, fission yeast, and plants, which suggests that it is critical to cell survival and proliferation. A role for COPS5 as a positive regulator of cellular proliferation is supported by evidence that it functionally inactivates several key tumor suppressors such as p53, RUNX3, Smad4, and p27Kip1 through altered subcellular localization, degradation, and deneddylation. These findings are underscored by the observation that COPS5 overexpression has been identified in a number of different tumor types and has been implicated in the initiation and progression of several types of cancer. Moreover, COPS5-deficient mice display an embryonically lethal phenotype highlighted by elevated expression of COPS5 targets such as p53 and p27.

References

[1] Wei, N. and Deng, X.W. (2003) Annu Rev Cell Dev Biol 19, 261-86.
[2] Kwok, S.F. et al. (1996) Plant Physiol 110, 731-42.
[3] Wei, N. et al. (1994) Cell 78, 117-24.
[4] Chamovitz, D.A. et al. (1996) Cell 86, 115-21.
[5] Cope, G.A. and Deshaies, R.J. (2003) Cell 114, 663-71.
[6] Claret, F.X. et al. (1996) Nature 383, 453-7.
[7] Wei, N. et al. (2008) Trends Biochem Sci 33, 592-600.
[8] Bech-Otschir, D. et al. (2001) EMBO J 20, 1630-9.
[9] Oh, W. et al. (2006) J Biol Chem 281, 17457-65.
[10] Wan, M. et al. (2002) EMBO Rep 3, 171-6.

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