6r7n

Structural highlights

Function

[CSN8_HUMAN] Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively.^{[1] [2] [3] [4] [5]} [CSN3_HUMAN] Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively.^{[6] [7] [8] [9] [10]} [CUL2_HUMAN] Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. May serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF). [CSN4_HUMAN] Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively.^{[11] [12] [13] [14] [15] [16]} [CSN1_HUMAN] Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Suppresses G-protein- and mitogen-activated protein kinase-mediated signal transduction.^{[17] [18] [19] [20] [21]} [ELOB_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).^{[22] [23]} The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.^{[24] [25]} [CSN2_HUMAN] Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Involved in early stage of neuronal differentiation via its interaction with NIF3L1.^{[26] [27] [28] [29] [30]} [ELOC_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).^[31] The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.^[32]

See Also

• Signalosome

References

1. ↑ Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998 Apr;12(6):469-78. PMID:9535219
2. ↑ Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 2001 Apr 2;20(7):1630-9. PMID:11285227 doi:http://dx.doi.org/10.1093/emboj/20.7.1630
3. ↑ Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001 May 18;292(5520):1382-5. Epub 2001 May 3. PMID:11337588 doi:http://dx.doi.org/10.1126/science.1059780
4. ↑ Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. PMID:12732143
5. ↑ Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech-Otschir D, Huang X, Berse M, Sperling J, Schade R, Dubiel W. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003 Mar 17;22(6):1302-12. PMID:12628923 doi:http://dx.doi.org/10.1093/emboj/cdg127
6. ↑ Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998 Apr;12(6):469-78. PMID:9535219
7. ↑ Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 2001 Apr 2;20(7):1630-9. PMID:11285227 doi:http://dx.doi.org/10.1093/emboj/20.7.1630
8. ↑ Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001 May 18;292(5520):1382-5. Epub 2001 May 3. PMID:11337588 doi:http://dx.doi.org/10.1126/science.1059780
9. ↑ Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. PMID:12732143
10. ↑ Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech-Otschir D, Huang X, Berse M, Sperling J, Schade R, Dubiel W. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003 Mar 17;22(6):1302-12. PMID:12628923 doi:http://dx.doi.org/10.1093/emboj/cdg127
11. ↑ Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998 Apr;12(6):469-78. PMID:9535219
12. ↑ Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 2001 Apr 2;20(7):1630-9. PMID:11285227 doi:http://dx.doi.org/10.1093/emboj/20.7.1630
13. ↑ Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001 May 18;292(5520):1382-5. Epub 2001 May 3. PMID:11337588 doi:http://dx.doi.org/10.1126/science.1059780
14. ↑ Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. PMID:12732143
15. ↑ Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech-Otschir D, Huang X, Berse M, Sperling J, Schade R, Dubiel W. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003 Mar 17;22(6):1302-12. PMID:12628923 doi:http://dx.doi.org/10.1093/emboj/cdg127
16. ↑ Granata A, Koo SJ, Haucke V, Schiavo G, Warner TT. CSN complex controls the stability of selected synaptic proteins via a torsinA-dependent process. EMBO J. 2011 Jan 5;30(1):181-93. doi: 10.1038/emboj.2010.285. Epub 2010 Nov 19. PMID:21102408 doi:http://dx.doi.org/10.1038/emboj.2010.285
17. ↑ Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998 Apr;12(6):469-78. PMID:9535219
18. ↑ Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 2001 Apr 2;20(7):1630-9. PMID:11285227 doi:http://dx.doi.org/10.1093/emboj/20.7.1630
19. ↑ Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001 May 18;292(5520):1382-5. Epub 2001 May 3. PMID:11337588 doi:http://dx.doi.org/10.1126/science.1059780
20. ↑ Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. PMID:12732143
21. ↑ Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech-Otschir D, Huang X, Berse M, Sperling J, Schade R, Dubiel W. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003 Mar 17;22(6):1302-12. PMID:12628923 doi:http://dx.doi.org/10.1093/emboj/cdg127
22. ↑ Garrett KP, Aso T, Bradsher JN, Foundling SI, Lane WS, Conaway RC, Conaway JW. Positive regulation of general transcription factor SIII by a tailed ubiquitin homolog. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7172-6. PMID:7638163
23. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
24. ↑ Garrett KP, Aso T, Bradsher JN, Foundling SI, Lane WS, Conaway RC, Conaway JW. Positive regulation of general transcription factor SIII by a tailed ubiquitin homolog. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7172-6. PMID:7638163
25. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
26. ↑ Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998 Apr;12(6):469-78. PMID:9535219
27. ↑ Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 2001 Apr 2;20(7):1630-9. PMID:11285227 doi:http://dx.doi.org/10.1093/emboj/20.7.1630
28. ↑ Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001 May 18;292(5520):1382-5. Epub 2001 May 3. PMID:11337588 doi:http://dx.doi.org/10.1126/science.1059780
29. ↑ Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. PMID:12732143
30. ↑ Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech-Otschir D, Huang X, Berse M, Sperling J, Schade R, Dubiel W. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003 Mar 17;22(6):1302-12. PMID:12628923 doi:http://dx.doi.org/10.1093/emboj/cdg127
31. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
32. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
33. ↑ Faull SV, Lau AMC, Martens C, Ahdash Z, Hansen K, Yebenes H, Schmidt C, Beuron F, Cronin NB, Morris EP, Politis A. Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome. Nat Commun. 2019 Aug 23;10(1):3814. doi: 10.1038/s41467-019-11772-y. PMID:31444342 doi:http://dx.doi.org/10.1038/s41467-019-11772-y