Antizyme inhibitor 1: a potential carcinogenic molecule

Abstract

Polyamines are multivalent and organic cations essential for cellular growth, proliferation, differentiation and apoptosis. Increased levels of polyamines are closely associated with numerous forms of cancer. An autoregulatory circuit composed by the ornithine decarboxylase(ODC), antizymes(AZ) and antizyme inhibitor (AZI) governs the intracellular level of polyamines. AZ binds with ODC to inhibit the ODC activity and to promote the ubiquitin-independent degradation of ODC. AZI binds to AZ with a higher affinity than ODC. Consequently, ODC is released from the ODC-AZ complex to rescue its activity. AZI increases the ODC activity to accelerate the formation of intracellular polyamines, triggering gastric and breast carcinogenesis as well as hepatocellular carcinoma and esophageal squamous cell carcinoma development. Especially, AZIN1, a primary member of AZI family, has aroused more attention because of its contributing to cancer. Even though its conformation is changed by the adenosine-to-inosine RNA editing, it plays an important role in tumorigenesis through regulating intracellular polyamines. Encouragingly, AZIN1 has been revealed to have an additional function outside the polyamine pathway so as to bypass the deficiency of targeting the polyamine biosynthetic pathway, promising to become a critical target for cancer therapy. Here, we congregate the latest advances on the AZIN1 and its potential contribution to carcinogenesis.

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