Abstract
Ornithine decarboxylase (ODC) initiates the polyamine biosynthetic pathway. The amount of ODC is altered in response to many growth factors, oncogenes, and tumor promoters and to changes in polyamine levels. Susceptibility to tumor development is increased in transgenic mice expressing high levels of ODC and is decreased in mice with reduced ODC due to loss of one ODC allele or elevated expression of antizyme, a protein that stimulates ODC degradation. This review describes key factors that contribute to the regulation of ODC levels, which can occur at the levels of transcription, translation, and protein turnover.
Highlights
L-Ornithine decarboxylase (ODC)2 catalyzes the first step in the polyamine biosynthetic pathway forming putrescine, which is converted into the polyamines spermidine and spermine [1,2,3,4] (Fig. 1)
The structure of the COOH-terminal region needed for rapid degradation of ODC is not known; this region is absent from the T. brucei and truncated mouse ODC structures that have been solved and is disordered in the crystal structure of the human ODC [8, 9]
Antizyme was first recognized as a non-competitive inhibitor of ODC that was synthesized in response to an increase in polyamine content [23]
Summary
Ornithine decarboxylase (ODC) initiates the polyamine biosynthetic pathway. The amount of ODC is altered in response to many growth factors, oncogenes, and tumor promoters and to changes in polyamine levels. This review describes key factors that contribute to the regulation of ODC levels, which can occur at the levels of transcription, translation, and protein turnover. Polyamine content plays important roles in both normal and neoplastic growth and alterations of polyamine synthesis via changes in ODC content occur in response to tumor promoters and carcinogens [2, 3]. ODC is very highly regulated, and ODC activity varies in response to many stimuli These alterations in activity are brought about by changes in the amount of ODC protein, which turns over very rapidly. Summaries of the vast literature describing earlier work on ODC, the myriad of factors altering its activity, and its value as a drug target are contained in previous reviews [2,3,4, 6]
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