Abstract
This review considers the role of bacterial antizyme in the regulation of polyamine biosynthesis and gives new perspectives on the involvement of antizyme in other significant cellular mechanisms. Antizyme is a protein molecule induced by the end product of the enzymic reaction that it inhibits, in a non-competitive manner. The bacterial ornithine decarboxylase is regulated by nucleotides, phosphorylation and antizyme. The inhibition of ornithine decarboxylase by antizyme can be relieved to different degrees by DNA or by a variety of synthetic nucleic acid polymers, attributed to a specific interaction between nucleic acid and antizyme. Recently, this interplay between bacterial antizyme and nucleic acid was determined by discerning an additional function to antizyme that proved to be the atoC gene product, encoding the response regulator of the bacterial two-component system AtoS-AtoC. The gene located just upstream of atoC encodes the sensor kinase, named AtoS, that modulates AtoC activity. AtoC regulates expression of atoDAEB operon which is involved in short-chain fatty acid metabolism. Antizyme is thus referred to as AtoC, functioning both as a post-translational and transcriptional regulator. Also, the AtoS-AtoC signal transduction system in E. coli has a positive regulatory role on poly-(R)-3-hydroxybutyrate biosynthesis. The properties and gene structural similarities of antizymes from different organisms were compared. It was revealed that conserved domains are present mostly in the C-domain of all antizymes. BLAST analysis of the E. coli antizyme protein (AtoC) showed similarities around 69–58% among proteobacteria, g-proteobacteria, enterobacteria and the thermophilic bacterium Thermus thermophilus. A working hypothesis is proposed for the metabolic role of antizyme (AtoC) describing the significant biological implications of this protein molecule. Whether antizymes exist to other enzymes in different tissues, meeting the criteria discussed in the text remains to be elucidated.
Highlights
The role of Az in various organisms Az was discovered by Canellakis and co-workers in rat liver and several cell lines
The induction of Az by exogenously added polyamines is inhibited by cycloheximide or puromycin, but not by actinomycin D indicating that polyamines induce antizyme by stimulating the translation of its mRNA [13]
Regulation of polyamine biosynthesis in bacteria Regulation of ornithine decarboxylase (ODC) allosterically by nucleotides Two ODCs, the biosynthetic and the biodegradative have been characterized in E. coli [33,34]
Summary
This review has evaluated some of the information available for the ornithine decarboxylase antizyme and has attempted to summarize the regulatory mechanisms in which it may be involved. Our understanding of the functions of Az derives from different biological sources. In eukaryotes three antizymes have been detected: i) Az1 functions as an inhibitory protein that targets its enzyme for degradation as well as a negative regulator of polyamine transport, ii) Az2 possesses very similar properties to Az1, except that it does not stimulate degradation of ODC and iii) Az3 is expressed only during spermatogenesis. The bacterial Az (AtoC) functions as an inhibitory protein to ODC, as well as transcriptional regulator for the two component AtoS-AtoC system. This two component system regulates the expression of atoDAEB
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