Vennela Tulluri, Venkatesh V Nemmara

Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA

Correspondence: Venkatesh V NemmaraDepartment of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USATel +1 856-256-5460Email nemmara@rowan.edu

Abstract: Polyamines are multivalent organic cations essential for many cellular functions, including cell growth, differentiation, and proliferation. However, elevated polyamine levels are associated with a slew of pathological conditions, including multiple cancers. Intracellular polyamine levels are primarily controlled by the autoregulatory circuit comprising two different protein types, Antizymes (OAZ) and Antizyme Inhibitors (AZIN), which regulate the activity of the polyamine biosynthetic enzyme ornithine decarboxylase (ODC). While OAZ functions to decrease the intracellular polyamine levels by inhibiting ODC activity and exerting a negative control of polyamine uptake, AZIN operates to increase intracellular polyamine levels by binding and sequestering OAZ to relieve ODC inhibition and to increase polyamine uptake. Interestingly, OAZ and AZIN exhibit autoregulatory functions on polyamine independent pathways as well. A growing body of evidence demonstrates the dysregulation of AZIN expression in multiple cancers. Additionally, RNA editing of the Azin1 transcript results in a gain-of-function phenotype, which is shown to drive aggressive tumor types. This review will discuss the recent advances in AZINs role in cancers via aberrant polyamine upregulation and its polyamine-independent protein regulation. This report will also highlight AZIN interaction with proteins outside the polyamine biosynthetic pathway and its potential implication to cancer pathogenesis. Finally, this review will reveal the protein interaction network of AZIN isoforms by analyzing three different interactome databases.

Keywords: polyamine, ornithine decarboxylase, antizyme inhibitor, antizyme, putrescine, spermine, spermidine, mRNA editing, 26S proteasome, degradation, ubiquitin-independent, protein interactome

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Read more:
Role of Antizyme Inhibitor Proteins in Cancers and Beyond | OTT - Dove Medical Press