Human ornithine decarboxylase-paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase

Kristiina Kanerva , Laura T. Mäkitie , Anna Pelander , Marja Heiskala , Leif C. Andersson (1)

1 Department of Pathology [Helsinki]

Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, is regulated by specific inhibitors, antizymes (AZ), which in turn are inhibited by antizyme inhibitor (AZI). We originally identified and cloned the cDNA for a novel human ODC-like protein called ornithine decarboxylase-paralogue (ODCp). Since ODCp was devoid of ODC catalytic activity, we proposed that ODCp is a novel form of AZI. ODCp has subsequently been suggested to function either as mammalian arginine decarboxylase (ADC) or as AZI in murine. Here we report that human ODCp is a novel AZI (AZI2). By using yeast two-hybrid screening and in vitro binding assay we show that ODCp binds AZ1-3. Measurements of ODC activity and ODC degradation assay reveal that ODCp inhibits AZ1 function as efficiently as AZI both in vitro and in vivo. We further demonstrate that the degradation of ODCp is ubiquitin-dependent and AZ1-independent similar to the degradation of AZI. We also show that human ODCp has no intrinsic ADC activity.

Mots clés: Life Sciences

Kristiina Kanerva, Laura T. Mäkitie, Anna Pelander, Marja Heiskala, Leif C. Andersson. Human ornithine decarboxylase-paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. Biochemical Journal, 2007, 409 (1), pp.187-192. ⟨10.1042/BJ20071004⟩. ⟨hal-00478855⟩