Posts Tagged ‘Neddylation’

Wikipedia Inaccuracies

Feb 10th, 2007

Oh dear. I like Wikipedia, its a lot of fun and usually reasonably accurate, but I just stumbled across an article which was almost entirely false. I can understand a few misconceptions sneaking in, but what possesses someone to write about a topic on which they clearly have no idea; especially when its something that specialist knowledge would seem a fairly obvious requirement.

The article in question was discussing the ubiquitin like protein Nedd8, something on which I’m currently doing a PhD. Ubiquitin is well characterised and has several roles, including targeting proteins to the proteasome, the ‘dustbin’ of the cell. Nedd8 is similar to Ubiquitin in structure, and the way it is used to tag other proteins. However it does not target proteins to the proteasome, and instead performs other functions. Yet the wikipedia article suggested that Nedd8 performed exactly the same role as ubiquitin, and accompanied this with ill formed sentences which gave little in the way of information and instead hinted at other severe misconceptions.

Neddylation is a protein degrading process analogous to ubiquitinylation in higher organisms (eukaryotes) in which NEDD8 is a key player. Unlike lysosomal degradation of proteins, a tagging occurs by attaching a small protein chain to mark for an enzyme complex (proteasome) by which they are then broken down. In fact, the term “neddylation” means a special form of ubiquitinylation initiated by an uncommon subset of proteins (see below), of which the initiators as well as the substrates are unique although the same pattern as in ubiquitinylation is followed.

So I have already addressed that Neddylation is not ‘a protein degrading process’ but furthermore neither is ubiquitination. The latter itself can result in protein degradation in some circumstances, but it itself is not protein degradation.

‘In which Nedd8 is a Key player.’ This badly formed sentence tells us little, and can serve to mislead. To suggest that Nedd8 is a key player in Neddylation is to suggest that bread is a ‘key player’ in a sandwich. Without the Nedd8 it simply isn’t Neddylation.

‘Unlike lysosomal degradation of proteins, a tagging occurs by attaching a small protein chain to mark for an enzyme complex (proteasome) by which they are then broken down.’ Surprisingly, if you can translate the sentence to English, this isn’t too objectionable; apart from the fact that it doesn’t belong here as Nedd8 doesn’t direct proteins to the proteasome. Furthermore as the sentence as it stands makes no sense, its possible that I’m just being charitable in my interpretation.

‘ In fact, the term “neddylation” means a special form of ubiquitinylation initiated by an uncommon subset of proteins (see below), of which the initiators as well as the substrates are unique although the same pattern as in ubiquitinylation is followed.’ A charitable reading could almost accept this, but its so garbled that such a reading is unlikely to occur to anyone not familiar with the subject. ‘A special form of ubiquitinylation’ is woolly at best. The process of Neddylation is analogous to that of ubiquitination (Or ubiquitylation, ubiquitinylation is a strange fusion of the two forms.*) and Nedd8 itself shows a great degree of homology (Similarity) to ubiquitin. But ultimately Neddylation is a ‘special form of ubiquitination’ in the same way a Renault is a special kind of Ford. It is misleading to say that the substrates are ‘unique’ as there are some targets which appear to be both Neddylated and Ubiquitinated in particular p53, however it would be true to say that their targets and target specificities are not identical. By initiators I will assume that the writer is referring to the enzyme cascade which leads to Neddylation. Again however they are incorrect, while the first two enzymes in the pathway, E1 and E2, are Nedd8 specific, no Nedd8 specific E3 ligases (the third enzyme) have been found, and it is suspected that the ubiquitin E3 ligases show dual specificity.

So ultimately there is only one idea in there which is remotely true, that ubiquitination and Neddylation are analogous processes. On reflection I get the impression that this is the only ‘fact’ the author knew.

I’ve pruned the article down to remove inaccuracies and will expand it later this week.

* Edited to add: Although a quick Google suggests this form isn’t completely unknown.

EDIT: I have closed this entry to comments as it was attracting a lot of spam.
[tags]science[/tags]