Antizyme 3 inhibits polyamine uptake and ornithine decarboxylase (ODC) activity, but does not stimulate ODC degradation.
Azs (antizymes) are small polyamine-induced proteins that function as feedback regulators of cellular polyamine homoeostasis. They bind to transient ODC (ornithine decarboxylase) monomeric subunits, resulting in inhibition of ODC activity and targeting ODC to ubiquitin-independent proteasomal degradation. Az3 is a mammalian Az isoform expressed exclusively in testicular germ cells and therefore considered as a potential regulator of polyamines during spermatogenesis. We show here that, unlike Az1 and Az2, which efficiently inhibit ODC activity and stimulate its proteasomal degradation, Az3 poorly inhibits ODC activity and fails to promote ODC degradation. Furthermore, Az3 actually stabilizes ODC, probably by protecting it from the effect of Az1. Its inhibitory effect is revealed only when it is present in excess compared with ODC. All three Azs efficiently inhibit the ubiquitin-dependent degradation of AzI (Az inhibitor) 1 and 2. Az3, similar to Az1 and Az2, efficiently inhibits polyamine uptake. The potential significance of the differential behaviour of Az3 is discussed.
Snapir
Zohar
Z
Department of Molecular Biology and Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Keren-Paz
Alona
A
Bercovich
Zippi
Z
Kahana
Chaim
C
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D055550:Protein Stability / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D020033:Protein Isoforms; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D046988:Proteasome Endopeptidase Complex; D009955:Ornithine Decarboxylase