Structural elements of the ubiquitin-independent proteasome degron of ornithine decarboxylase.
Mouse ODC (ornithine decarboxylase) is quickly degraded by the 26S proteasome in mammalian and fungal cells. Its degradation is independent of ubiquitin but requires a degradation signal composed of residues 425-461 at the ODC C-terminus, cODC (the last 37 amino acids of the ODC C-terminus). Mutational analysis of cODC revealed the presence of two essential elements in the degradation signal. The first consists of cysteine and alanine at residues 441 and 442 respectively. The second element is the C-terminus distal to residue 442; it has little or no sequence specificity, but is intolerant of insertions or deletions that alter its span. Reducing conditions, which preclude all well-characterized chemical reactions of the Cys(441) thiol, are essential for in vitro degradation. These experiments imply that the degradative function of Cys(441) does not involve its participation in chemical reaction; it, instead, functions within a structural element for recognition by the 26S proteasome.
Takeuchi
Junko
J
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
Chen
Hui
H
Hoyt
Martin A
MA
Coffino
Philip
P
D019943:Amino Acid Substitution; D000818:Animals; D007700:Kinetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012156:Reticulocytes / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D025801:Ubiquitin / Q000378:metabolism*
D011994:Recombinant Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D009955:Ornithine Decarboxylase