The appearance of an ornithine decarboxylase inhibitory protein upon the addition of putrescine to cell cultures

Fong, Wang‐Fun; Heller, J; Canellakis, E.S.

doi:10.1016/0304-4165(76)90054-4

Cited by 256 publications

(121 citation statements)

References 11 publications

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“…We identified this band as Zl antizyme because of its co-migration with ZI antizyme produced both by translation in vitro and by bacterial expression. Consistent with the known instability of antizyme [5,6], the ZI band was not found in the 7 h samples of dexamethasone-treated cells that received cycloheximide at 4 h (last lane, Figure 2b). ODC protein levels were visibly diminished in the samples of HZ7 cells exposed to dexamethasone or cycloheximide, and were almost undetectable in samples of cultures receiving both treatments.…”

Section: Resultssupporting

confidence: 74%

“…Since excessive polyamines are detrimental to normal cell function [4], both polyamine biosynthesis and transport are tightly feedback-regulated. Substantial progress has been made in understanding feedback repression of polyamine biosynthesis, which appears to centre around the polyamine-stimulated production of a labile protein, antizyme, that binds specifically and reversibly to the initial enzyme in polyamine synthesis, ornithine decarboxylase (ODC) [5][6][7][8][9][10]. Experiments in vitro have revealed that this ODC-antizyme complex is sensitive to rapid degradation by the 26 S proteasome [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells

Mitchell

Judd

Bareyal-Leyser

et al. 1994

Biochemical Journal

207

156

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Antizyme, a spermidine-induced protein that binds and stimulates ornithine decarboxylase degradation, is now shown also to mediate the rapid feedback inhibition of polyamine uptake into mammalian cells. Using a cell line (HZ7) transfected with truncated antizyme cDNA, and mutant ornithine decarboxylase cell lines, we demonstrate that this newly discovered action of antizyme is distinct from its role in modulating polyamine biosynthesis.

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Section: Resultssupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells

Mitchell

Judd

Bareyal-Leyser

et al. 1994

Biochemical Journal

207

156

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“…Indirect amine inhibitors of omithine decarboxylase (such as 1,3-diaminopropane), which may act through an induction of protein inhibitors to the enzyme [30] or through more direct transcriptional or translational control mechanisms [31 ], have likewise been employed to abolish polyamine accumulation in regenerating rat liver [7][8][9], in rat liver during refeeding [32] and ovary cells grown in culture [33]. In every instance, the prevention of enhanced spermidine and/or putrescine accumulation was associated with distinct decreases in the synthesis of DNA.…”

Section: Discussionmentioning

confidence: 99%

Reversible inhibition of rat liver regeneration by 1,3‐diamino‐2‐propanol, an inhibitor of ornithine decarboxylase

1978

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“…Polyamines are ubiquitous organic cations with tightly regulated cellular concentrations and are essential for cell growth and development (1,2). Antizyme (AZ) 1 was first described as an inhibitor of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis (3).…”

mentioning

confidence: 99%

Identification of Nuclear Export Signals in Antizyme-1

Murai

Murakami

Matsufuji

2003

Journal of Biological Chemistry

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Antizyme-1 (AZ1) is a protein that negatively regulates polyamine synthesis by inhibiting the key synthetic enzyme ornithine decarboxylase and targeting it for degradation by the 26 S proteasome. Recent work shows that antizyme protein translocates to the nucleus during mouse development (Gritli-Linde, A., Nilssom, J., Bohlooly, Y. M., Heby, O., and Linde, A. (2001) Dev. Dyn. 220, 259 -275). However, the significance and mechanism of this phenomenon remain unclear. In this study, we expressed AZ1 fused with enhanced green fluorescent protein (EGFP) to study its localization in a living cell. We found that EGFP-AZ1 was predominantly localized in the cytoplasm and that treatment with leptomycin B, a specific inhibitor of chromosomal region maintenance 1 (CRM1) induced nuclear accumulation of EGFP-AZ1 in Chinese hamster ovary and NIH3T3 cells. Two independent nuclear export signal (NES) sequences, each containing essential hydrophobic residues, were identified in the 50 N-terminal amino acid residues and in the central part of AZ1. The activity of the second NES was inhibited by an N-terminal adjacent region and was only revealed in N-terminal truncated constructs. Both NESs were active when fused to an artificial nuclear protein SV40-NLS-EGFP-EGFP. The ability of AZ1 to shuttle between the nucleus and the cytoplasm suggests that it has a novel function in the nucleus.Polyamines are ubiquitous organic cations with tightly regulated cellular concentrations and are essential for cell growth and development (1, 2). Antizyme (AZ) 1 was first described as an inhibitor of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis (3). When cellular polyamine levels rise, AZ is induced and then binds to the monomeric form of ODC (4, 5), which makes the enzyme a preferential substrate for proteolysis by the 26 S proteasome without ubiquitination (6). AZ also inhibits the uptake of extracellular polyamines (7,8). There are at least three independent antizyme isoforms conserved among mammals. AZ1 and AZ2 have a wide tissue distribution, whereas AZ3 is testis-specific (9, 10). Expression of AZs is induced by a unique translational frameshift mechanism (11). For AZ1, when cellular polyamine levels are low, the polypeptide corresponding to amino acid residues 1-68 is produced and translation is terminated at the following UGA codon (11). When cellular polyamine levels are high, ϩ1 frameshifting occurs after the 68th codon is decoded, resulting in the full-length antizyme protein (amino acid residues 1-227). All of the known regulatory activities of AZ1 are present in amino acid residues 69 -227 (12). A second AUG exists in AZ1 mRNA at the 34th codon, and this second AUG is also utilized as initiation codon (11, 13). The two resulting translation products have different half-lives (14). Furthermore, it has been suggested that the N-terminal region of the translation product from the first AUG contains a putative mitochondrial targeting signal and thus the distribution of AZ1 may depend on this region (15). It is curre...

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The appearance of an ornithine decarboxylase inhibitory protein upon the addition of putrescine to cell cultures

Cited by 256 publications

References 11 publications

Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells

Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells

Reversible inhibition of rat liver regeneration by 1,3‐diamino‐2‐propanol, an inhibitor of ornithine decarboxylase

Identification of Nuclear Export Signals in Antizyme-1

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