Antizyme inhibitor: mysterious modulator of cell proliferation

Abstract

In contrast to the considerable interest in the oncogene ornithine decarboxylase (ODC) and in the family of antizymes with regard to cell proliferation and tumorigenesis, the endogenous antizyme inhibitor (AZI) has been less well studied. AZI is highly homologous to the enzyme ODC but does not possess any decarboxylase activity. Elevated ODC activity is associated with most forms of human malignancies. Antizymes bind ODC, inhibit ODC activity and promote the ubiquitin-independent degradation of ODC. Consequently they are proposed as tumor suppressors. In particular, the most studied member of the antizyme family, antizyme 1, has been demonstrated to play a role in tumor suppression. AZI inactivates all members of the antizyme family, reactivates ODC and prevents the proteolytic degradation of ODC, which may suggest a role for AZI in tumor progression.

Allosteric regulation of an essential trypanosome polyamine biosynthetic enzyme by a catalytically dead homolog

“…Ornithine decarboxylase in mammalian and yeast cells is regulated by a protein inhibitor termed antizyme, which appears to be a duplication of a catabolic enzyme in the pathway, spermine-spermidine N 1 -acetyltransferase (35). Antizyme is, in turn, regulated by antizyme inhibitor, which is itself a pseudoenzyme, having arisen by gene duplication of ornithine decarboxylase, followed by loss of catalytic activity (36). The polyamine pathway thus provides a paradigm for the evolution of metabolic pathways and their regulation by gene duplication and divergence.…”

Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A

“…The results presented here suggest that Az1 might play the targeting role in the Ub-independent degradation of Aurora-A. To investigate whether there exists any functional link between AURKAIP1 and Az1, we exploited the Az inhibitor (AzI), a physiological regulator of the Az family (Mangold, 2006). High AzI level downregulates Azmediated degradation of ODC as well as polyamine transport (Coffino, 2001).…”

Polyamines and transglutaminases: future perspectives

“…AZIs interfere with antizyme functions, leading to increased polyamine biosynthesis, increased cell proliferation, as well as enhanced cell transformation and tumorigenesis (Keren-Paz et al 2006;Mangold 2006). Murakami et al (2014) provide evidence that multiple forms of mouse AZIN1 mRNA are differentially regulated by polyamines.…”