The antizyme family: polyamines and beyond.
The family of antizymes functions as regulators of polyamine homeostasis. They are a class of small, inhibitory proteins, whose expression is regulated by a unique ribosomal frameshift mechanism. They have been shown to inhibit cell proliferation and possess anti-tumor activity. Antizymes bind ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis. They inhibit its enzymatic activity and promote the ubiquitin-independent degradation of ODC by the 26S proteasome. In addition, they also negatively regulate polyamine transport. Antizyme-mediated, ubiquitin-independent degradation of ODC is conserved from yeast to man. But recent data suggest that this degradation pathway might not be restricted to ODC alone and could involve newly discovered antizyme binding partners. Interestingly, antizyme proteins have been strictly preserved over a vast evolutionary timeframe. Antizymes consequently represent an important class of proteins that regulate cell growth and metabolism by a diverse set of mechanisms that include protein degradation, inhibition of enzyme activity, small molecule transport and other, potentially not yet discovered properties.
Mangold
Ursula
U
Program in Vascular Biology, Department of Surgery, Children's Hospital, Boston, MA 02115, USA. ursula.mangold@childrens.harvard.edu
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000502:physiology
D002352:Carrier Proteins; D029721:Drosophila Proteins; C507133:Oda protein, Drosophila; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011506:Proteins; D025801:Ubiquitin; C031017:ornithine decarboxylase antizyme; C039317:ornithine decarboxylase antizyme inhibitor; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease