Signals for proteolysis

Dr. David J. Meyer meyerdj at phibred.com
Wed Aug 25 11:56:44 EST 1999

"Evangelos Christodoulou" <echristo at biology.db.uoa.gr> wrote:

>> Is there a way of finding if a certain protein is likely to be short-lived
>> in a cell just by looking at the amino acid sequence? When making a
>> literature search, I have found many papers that mention an "N-end rule"
>> but I haven't been able to figure out what that is beyond knowing that a
>> Lys residue is needed for binding of ubiquitin. Besides, I got the
>> impresion that these signalling domains can be both at the N or the
>> C-terminus in a protein but I don't know if they are different. By the way,
>> I work in yeast, in case this makes a great difference in the way the
>> proteins are processed (as you can see, I haven't got much idea about all
>> these processes, sorry!)
>> Could someone point me to a good www site for analysing my protein sequence
>> and find if its turnover is likely to be rapid? Alternatively, anybody
>> knows of a review that deals with domains in a protein that signal it for
>> degradation?


>Evangelos Christodoulou
>University of Athens, Greece
>If Che Guevara was alive he'd use a Mac
>-the only revolutionary-friendly platform

SignalP is used to predict N-terminal ER-targeting signal sequences,
not what the original poster was looking for.

If you look at Varshavsky's papers carefully, you will learn that the
N-end rule has to do with what the N-terminal residue is. Some
residues were determined to confer short half-lives, others long
half-lives. The degradation appears to be via the ubiquitin-proteasome
pathway. "Stabilizing" and "destabilizing" residues have been
determined in both E. coli and S. cerevisiae.

Hope this helps, although the world of protein folding and turnover is
much more complicated than any algorithm to predict expression levels
might indicate!

David J. Meyer, Ph.D.
Quality Traits
Pioneer Hi-Bred International, Inc.
7300 NW 62nd Ave.
Johnston, IA   50131-1004

Ph. 515/254-2639
FAX 515/254-2619
Email: meyerdj at phibred.com

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