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NEDD8

Definition:

Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis via its conjugation to a limited number of cellular proteins, such as cullins or p53/TP53. Attachment of NEDD8 to cullins is critical for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, thus facilitating polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. Attachment of NEDD8 to p53/TP53 inhibits p53/TP53 transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M.

References:

[1]. F Osaka, et al. A new NEDD8-ligating system for cullin-4A. Genes Dev. 1998 Aug 1;12(15):2263-8. [Content Brief]

[2]. T Hori, et al. Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene. 1999 Nov 18;18(48):6829-34. [Content Brief]

[3]. Dimitris P Xirodimas, et al. Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell. 2004 Jul 9;118(1):83-97. [Content Brief]

[4]. Jixin Cui, et al. Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family. Science. 2010 Sep 3;329(5996):1215-8. [Content Brief]

[5]. Helen Walden, et al. The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Mol Cell. 2003 Dec;12(6):1427-37. [Content Brief]

[6]. Ruthie E Amir, et al. 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. [Content Brief]

[7]. D Liakopoulos, et al. 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. [Content Brief]

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