The Cop9 Signalosome (CSN)

(a.k.a the COP9 complex, Jab1-containing signalosome, Signalosome)

Short History

The CSN was first identified as an essential negative regulator of photomorphogenesis in Arabidopsis(1). An 8-subunit complex, originally named the COP9 complex, was purified from cauliflower in 1996 (2). One of the subunits, then called JAB1, and now referred to as CSN5, was independently identified several times due its interaction with several key signaling molecules. In 1998, a mammalian complex highly conserved with the plant CSN was published(3)(4). Subsequent identification and characterization of the CSN from Drosophila(5), budding(6) and fission yeast(7), Aspergillus nidulans, Dictyostelium and C. elegans highlighted its role as a general modulator of diverse cellular and developmental processes. In plants, insects and animals the complex has eight subunits, while in C. elegans there are seven, in S. pombe six, and in S. cerevicea, five. Taking into account this high conservation among diverse species, the CSN community agreed upon a common CSN nomenclature, with the subunits renamed CSN1 - CSN8 (8).

What does it do?

The CSN is involvolved in multiple biologucal rocesses, including:

DeNeddylation

AssociatedKinases

DeUbiquitynilation

SubCellular localization

Small Jab1Complexes

CSN in cancer

Subunits

The links in the first column take you to a new page for each subunit, where you'll find information and links to:

• homologs
• interacting proteins
• modifications
• mutants, etc. The links under each organism open specifc gene information.

Proteins whose stability is CSN-dependent

Mutants

Notes

1 : Wei, N., Chamovitz, D.A., and Deng, X.W. (1994). Arabidopsis COP9 is a component of a novel signaling complex mediating light control of development. Cell 78, 117-124.

2 : Chamovitz, D.A., Wei, N., Osterlund, M.T., von Arnim, A.G., Staub, J.M., Matsui, M., and Deng, X.W. (1996). The COP9 complex, a novel multisubunit nuclear regulator involved in light control of a plant developmental switch. Cell 86, 115-121.

3 : Wei, N., Tsuge, T., Serino, G., Dohmae, N., Takio, K., Matsui, M., and Deng, X.W. (1998). Conservation of the COP9 complex between plants and mammals and its relationship to the 26S proteasome regulatory complex. Curr Biol 8, 919-922.

4 : Seeger, M., Kraft, R., Ferrell, K., Bech-Otschir, D., Dumdey, R., Schade, R., Gordon, C., Naumann, M., and Dubiel, W. (1998). A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. Faseb J 12, 469-478.

5 : Freilich S, Oron E, Kapp Y, Nevo-Caspi Y, Orgad S, Segal D, Chamovitz DA (1999) The COP9 signalosome is essential for development of Drosophila melanogaster.Curr Biol 9: 1187-1190

6 : Maytal-Kivity, V., Piran, R., Pick, E., Hofmann, K., and Glickman, M.H. (2002). COP9 signalosome components play a role in the mating pheromone response of S. cerevisiae. EMBO Rep 3, 1215-1221.

7 , 35 : Mundt, K.E., Porte, J., Murray, J.M., Brikos, C., Christensen, P.U., Caspari, T., Hagan, I.M., Millar, J.B., Simanis, V., Hofmann, K., et al. (1999). The COP9/signalosome complex is conserved in fission yeast and has a role in S phase. Curr Biol 9, 1427-1430.

8 : Deng, X.W., Dubiel, W., Wei, N., Hofmann, K., Mundt, K., Colicelli, J., Kato, J., Naumann, M., Segal, D., Seeger, M., et al. (2000). Unified nomenclature for the COP9 signalosome and its subunits: an essential regulator of development Trends Genet 16, 202-203.

9 : Yahalom, A., Kim, T.H., Roy, B., Singer, R., von Arnim, A.G., and Chamovitz, D.A. (2008). Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein translation. Plant J 53, 300-311.

10 : Knowles, A., Koh, K., Wu, J.T., Chien, C.T., Chamovitz, D.A., and Blau, J. (2009). The COP9 signalosome is required for light-dependent timeless degradation and Drosophila clock resetting. J Neurosci 29, 1152-1162.

11 , 12 , 14 , 18 : Oron E, Mannervik M, Rencus S, Harari-Steinberg O, Neuman-Silberberg S, Segal D, Chamovitz DA (2002) COP9 signalosome subunits 4 and 5 regulate multiple pleiotropic pathways in Drosophila melanogaster. Development 129: 4399-4409.

13 : Harari-Steinberg O, Cantera R, Denti S, Bianchi E, Oron E, Segal D, Chamovitz DA (2007) COP9 signalosome subunit 5 (CSN5/Jab1) regulates the development of the Drosophila immune system: effects on Cactus, Dorsal and hematopoiesis. Genes Cells 12: 183-195

15 : Suh GSB, Poeck B, Chouard T, Oron E, Segal D, Chamovitz DA, Zipursky SL (2002) Drosophila JAB1/CSN5 acts in photoreceptor cells to induce glial cells. Neuron 33: 35-46

16 : Oron E, Tuller T, Li L, Rozovsky N, Yekutieli D, Rencus-Lazar S, Segal D, Chor B, Edgar BA, Chamovitz DA (2007) Genomic analysis of COP9 signalosome function in Drosophila melanogaster reveals a role in temporal regulation of gene expression. Mol Syst Biol 3: 108

17 : Freilich S, Oron E, Kapp Y, Nevo-Caspi Y, Orgad S, Segal D, Chamovitz DA (1999) The COP9 signalosome is essential for development of Drosophila melanogaster. Curr Biol 9: 1187-1190

19 : Doronkin S, Djagaeva I, Beckendorf SK (2002) CSN5/Jab1 mutations affect axis formation in the Drosophila oocyte by activating a meiotic checkpoint. Development 129: 5053-5064.

20 : Oren-Giladi P, Krieger O, Edgar BA, Chamovitz DA, Segal D (2008) Cop9 signalosome subunit 8 (CSN8) is essential for Drosophila development. Genes Cells 13: 221-231

21 : Wei, N., Kwok, S.F., von Arnim, A.G., Lee, A., Mcnellis, T.W., Piekos, B., and Deng, X.W. (1994). Arabidopsis COP8, COP10, and COP11 genes are involved in repression of photomorphogenic development in darkness. Plant Cell 6, 629-643.

22 : Serino, G., Su, H., Peng, Z., Tsuge, T., Wei, N., Gu, H., and Deng, X.W. (2003). Characterization of the last subunit of the Arabidopsis COP9 signalosome: implications for the overall structure and origin of the complex. Plant Cell 15, 719-731.

23 : Peng, Z., Serino, G., and Deng, X.W. (2001). A role of Arabidopsis COP9 signalosome in multifaceted developmental processes revealed by the characterization of its subunit 3. Development 128, 4277-4288.

24 : Serino, G., Tsuge, T., Kwok, S., Matsui, M., Wei, N., and Deng, X.W. (1999). Arabidopsis cop8 and fus4 mutations define the same gene that encodes subunit 4 of the COP9 signalosome. Plant Cell 11, 1967-1980.

25 , 28 : Dohmann, E.M., Kuhnle, C., and Schwechheimer, C. (2005). Loss of the CONSTITUTIVE PHOTOMORPHOGENIC9 signalosome subunit 5 is sufficient to cause the cop/det/fus mutant phenotype in Arabidopsis. Plant Cell 17, 1967-1978.

26 , 29 : Gusmaroli, G., Feng, S., and Deng, X.W. (2004). The Arabidopsis CSN5a and CSN5b subunits are present in distinct COP9 signalosome complexes, and mutations in their JAMM domains exhibit differential dominant negative effects on development. Plant Cell 16, 2984-3001.

27 , 30 , 31 , 32 : Gusmaroli, G., Figueroa, P., Serino, G., and Deng, X.W. (2007). Role of the mpn subunits in COP9 signalosome assembly and activity, and their regulatory interaction with Arabidopsis Cullin3-based E3 ligases. Plant Cell 19, 564-581.

33 : Karniol, B., Malec, P., and Chamovitz, D.A. (1999). Arabidopsis FUSCA5 encodes a novel phosphoprotein that is a component of the COP9 complex. Plant Cell 11, 839-848.

34 : Wei, N., and Deng, X.W. (1992). COP9: a new genetic locus involved in light-regulated development and gene expression in arabidopsis. Plant Cell 4, 1507-1518.

36 , 37 , 38 : Mundt, K.E., Liu, C., and Carr, A.M. (2002). Deletion Mutants in COP9/Signalosome Subunits in Fission Yeast Schizosaccharomyces pombe Display Distinct Phenotypes. Mol Biol Cell 13, 493-502.

39 : Smith, P., Leung-Chiu, W.M., Montgomery, R., Orsborn, A., Kuznicki, K., Gressman-Coberly, E., Mutapcic, L., and Bennett, K. (2002). The GLH proteins, Caenorhabditis elegans P granule components, associate with CSN-5 and KGB-1, proteins necessary for fertility, and with ZYX-1, a predicted cytoskeletal protein. Dev Biol 251, 333-347.

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