Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome

Microbial Cell

R. Jürgen Dohmen¹  Daniela Gödderz¹  R. Roshini Beenukumar¹  R. Palanimurugan¹ 

[1] Institute for Genetics, University of Cologne, Biocenter, Zülpicher Str. 47a, D-50674 Cologne, Germany.;

关键词: antizyme;    ODC;    polyamines;    proteasome;    ubiquitin;   

DOI  :  10.15698/mic2015.06.206

来源: DOAJ

【 摘 要 】

Ornithine decarboxylase (ODC), a ubiquitin-independent substrate of the proteasome, is a homodimeric protein with a rate-limiting function in polyamine biosynthesis. Polyamines regulate ODC levels by a feedback mechanism mediated by ODC antizyme (OAZ). Higher cellular polyamine levels trigger the synthesis of OAZ and also inhibit its ubiquitin-dependent proteasomal degradation. OAZ binds ODC monomers and targets them to the proteasome. Here, we report that polyamines, aside from their role in the control of OAZ synthesisandstability,directlyenhanceOAZ-mediatedODCdegradationby theproteasome.UsingastablemutantofOAZ,weshowthatpolyamines promote ODC degradation in Saccharomyces cerevisiae cells even when OAZ levels are not changed. Furthermore, polyamines stimulated the in vitro degradationofODCbytheproteasomeinareconstitutedsystemusingpurified components.Intheseassays,spermineshowsagreatereffectthanspermidine. By contrast, polyamines do not have any stimulatory effect on the degradation of ubiquitin-dependent substrates.

【 授权许可】

Unknown