1xt9

Structural highlights

Function

[SENP8_HUMAN] Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.^{[1] [2] [3] [4] [5]} [NEDD8_HUMAN] Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.^{[6] [7] [8]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• NEDD8
• Sentrin-specific protease

References

1. ↑ Mendoza HM, Shen LN, Botting C, Lewis A, Chen J, Ink B, Hay RT. NEDP1, a highly conserved cysteine protease that deNEDDylates Cullins. J Biol Chem. 2003 Jul 11;278(28):25637-43. Epub 2003 May 1. PMID:12730221 doi:http://dx.doi.org/10.1074/jbc.M212948200
2. ↑ Wu K, Yamoah K, Dolios G, Gan-Erdene T, Tan P, Chen A, Lee CG, Wei N, Wilkinson KD, Wang R, Pan ZQ. DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1. J Biol Chem. 2003 Aug 1;278(31):28882-91. Epub 2003 May 19. PMID:12759363 doi:http://dx.doi.org/10.1074/jbc.M302888200
3. ↑ Gan-Erdene T, Nagamalleswari K, Yin L, Wu K, Pan ZQ, Wilkinson KD. Identification and characterization of DEN1, a deneddylase of the ULP family. J Biol Chem. 2003 Aug 1;278(31):28892-900. Epub 2003 May 19. PMID:12759362 doi:http://dx.doi.org/10.1074/jbc.M302890200
4. ↑ Xirodimas DP, Saville MK, Bourdon JC, Hay RT, Lane DP. Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell. 2004 Jul 9;118(1):83-97. PMID:15242646 doi:http://dx.doi.org/10.1016/j.cell.2004.06.016
5. ↑ Shen LN, Liu H, Dong C, Xirodimas D, Naismith JH, Hay RT. Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. EMBO J. 2005 Apr 6;24(7):1341-51. Epub 2005 Mar 17. PMID:15775960
6. ↑ Liakopoulos D, Busgen T, Brychzy A, Jentsch S, Pause A. Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5510-5. PMID:10318914
7. ↑ Hori T, Osaka F, Chiba T, Miyamoto C, Okabayashi K, Shimbara N, Kato S, Tanaka K. Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene. 1999 Nov 18;18(48):6829-34. PMID:10597293 doi:http://dx.doi.org/10.1038/sj.onc.1203093
8. ↑ Amir RE, Iwai K, Ciechanover A. The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105. J Biol Chem. 2002 Jun 28;277(26):23253-9. Epub 2002 Apr 12. PMID:11953428 doi:http://dx.doi.org/10.1074/jbc.M200967200
9. ↑ Reverter D, Wu K, Erdene TG, Pan ZQ, Wilkinson KD, Lima CD. Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1. J Mol Biol. 2005 Jan 7;345(1):141-51. PMID:15567417 doi:10.1016/j.jmb.2004.10.022