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Amino acids regulate expression of Antizyme‐1 and modulate Ornithine Decarboxylase Activation
Author(s) -
Ray Ramesh M,
Viar Mary Jane,
Johnson Leonard R.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1010.5
Subject(s) - ornithine decarboxylase , cycloheximide , ornithine decarboxylase antizyme , amino acid , biochemistry , asparagine , phosphorylation , protein biosynthesis , chemistry , glutamine , microbiology and biotechnology , biology , enzyme
In a glucose‐salt solution (EBSS), asparagine (ASN) stimulates ornithine decarboxylase (ODC) activity in a dose‐dependent manner. We determined the mechanism by which ASN induces ODC activity. In the absence of amino acids (AA), an antizyme 20‐kDa isoform (AZ‐1‐20), which inhibits ODC activity, increased in a time‐dependent fashion. ASN prevented the accumulation of AZ‐1‐20 and rapidly induced ODC activity, as did glutamine and α‐ a mino i so b utyric acid. In contrast, lysine and valine induced AZ‐1‐20 expression and decreased ASN‐induced ODC activity. ODC induction by ASN was lower in DMEM containing AA as compared to that in DMEM without AA, suggesting that AZ‐1‐20‐inducing AA may partially neutralize the effect of ASN. Incubation in EBSS for 6 hrs increased AZ‐1‐20 protein levels, and addition of ASN decreased accumulated AZ‐1‐20. Cycloheximide similarly caused elimination of accumulated AZ‐1‐20 but did not alter the rate of decrease due to ASN. Actinomycin‐D failed to prevent AZ‐1‐20 expression in EBSS. These results suggest that ASN modulates AZ‐1‐20 levels by regulating synthesis. ASN prevented the phosphorylation and caused accumulation of eukaryotic initiation factor binding protein (4EBP1). Thus, by preventing the phosphorylation of 4EBP1, ASN causes it to accumulate and bind to eIF4E resulting in the inhibition of the synthesis of AZ‐1‐20, allowing the activation of ODC.