DENEDDYLASE1 Deconjugates NEDD8 from Non-Cullin Protein Substrates in Arabidopsis thaliana. Issue 3 (17th March 2015)

• Record Type: Journal Article
• Authors: Mergner, Julia; Heinzlmeir, Stephanie; Kuster, Bernhard; Schwechheimer, Claus
• Is Part Of: The Plant Cell. Volume 27:Issue 3(2015)
• Page Start: 741
• Page End: 753
• Publication Date: 2015-03-17
• DOI: 10.1105/tpc.114.135996
• Languages: English
• ISSNs: 1040-4651

Abstract

Abstract : Mutants of an Arabidopsis DENEDDYLASE1 accumulate a broad range of NEDD8 conjugates, including AUXIN RESISTANT1, thus showing the existence of many NEDD8 conjugates in addition to the cullins. Abstract: The evolutionarily conserved 8-kD protein NEDD8 (NEURAL PRECURSOR CELL EXPRESSED, DEVELOPMENTALLY DOWN-REGULATED8) belongs to the family of ubiquitin-like modifiers. Like ubiquitin, NEDD8 is conjugated to and deconjugated from target proteins. Many targets and functions of ubiquitylation have been described; by contrast, few targets of NEDD8 have been identified. In plants as well as in non-plant organisms, the cullin subunits of cullin-RING E3 ligases are NEDD8 conjugates with a demonstrated functional role for the NEDD8 modification. The existence of other non-cullin NEDD8 targets has generally been questioned. NEDD8 is translated as a precursor protein and proteolytic processing exposes a C-terminal glycine required for NEDD8 conjugation. In animals and yeast, DENEDDYLASE1 (DEN1) processes NEDD8. Here, we show that mutants of a DEN1 homolog from Arabidopsis thaliana have no detectable defects in NEDD8 processing but do accumulate a broad range of NEDD8 conjugates; this provides direct evidence for the existence of non-cullin NEDD8 conjugates. We further identify AUXIN RESISTANT1 (AXR1), a subunit of the heterodimeric NEDD8 E1 activating enzyme, as a NEDD8-modified protein in den1 mutants and wild type and provide evidence that AXR1 function may be compromised in the absence of DEN1 activity. Thus, in plants, neddylation may serve as a regulatory mechanism for cullin and non-cullin proteins.