Posttranscriptional regulation of ornithine decarboxylase activity

Dircks, Lori K.; Grens, Ann; Slezynger, Thelma C.; Scheffler, Immo E.

doi:10.1002/jcp.1041260307

Cited by 62 publications

(19 citation statements)

References 30 publications

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“…Our findings are in agreement with an earlier study demonstrating an ATP requirement for the decay of ODC activity [45]. However, they contradict two recent studies which concluded that ODC degradation is an ATP-independent process [46, 471. It is unclear how we can reconcile our conclusions and those of one of the other studies [46], as in each case a similar experimental approach was utilized. In the study of Glass and Gerner [47], however, clear experimental support for such a conclusion was not provided.…”

Section: Discussionmentioning

confidence: 79%

Degradation of ornithine decarboxylase in mammalian cells is ATP dependent but ubiquitin independent

Rosenberg-Hasson

Bercovich

Ciechanover

et al. 1989

European Journal of Biochemistry

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Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines in mammalian cells is characterized by an extremely short half-life. In the present study, ODC degradation was investigated in 653-1 mouse myeloma cells that overproduce ODC and in ts85 cells that are thermosensitive for conjugation of ubiquitin to target proteins. Addition of 2-deoxyglucose and dinitrophenol (agents that efficiently deplete cellular ATP) to the growth medium of these cells inhibited ODC degradation. In contrast, chloroquine and leupeptin, inhibitors of intralysosomal proteolysis, did not affect ODC degradation. Shifting ts85 cells to 42 "C (a non-permissive temperature that inhibited conjugation of ubiquitin to target proteins) did not prevent ODC degradation. The ATP-dependent degradation of ODC in 653-1 cells was inhibited substantially by N"-tosyl-L-lysine chloromethane (TosPheMeCl), iodoacetamide and o-phenanthroline. These results suggest that ODC degradation occurs via a non-lysosomal, ATP-requiring and ubiquitin-independent cellular proteolytic mechanism, and that serine proteases and enzymes containing sulphydryl groups and metalloenzyme(s) may be involved in this process.Ornithine decarboxylase is a key enzyme in the biosynthetic pathway of polyamines in mammalian cells 111. This pyridoxal-phosphate-dependent enzyme that decarboxylates ornithine to form putrescine is characterized by a high turnover rate [2] and by a rapid and dramatic induction in response to stimulation by a variety of growth stimuli [3,4]. Accumulating evidence suggests that ODC expression is regulated at several levels: production of mRNA [5-91, changes in the efficiency of mRNA translation [lo ~ 121, changes in protein stability [I 31 and by posttranslational modifications and interactions [lo, 11, 14-161. The extremely short half-life of ODC permits rapid adjustment of its activity by these regulatory mechanisms.The mechanisms involved in intracellular protein degradation are still poorly understood. Nevertheless, it is widely accepted that lysosomes are involved in degradation of endocytosed proteins and of cellular proteins under conditions of nutritional deprivation [17 -191. In contrast, nonlysosomal ATP-requiring pathways are engaged in selective degradation of short-lived proteins under normal metabolic conditions [17 -191. While the multiplicity of distinct nonlysosomal proteolytic mechanisms in mammalian cells is still unknown, a non-lysosomal ATP-dependent proteolytic system has been characterized and partially purified from rabbit reticulocytes [20,21]. This proteolytic system contains several essential components; among them the ubiquitin polypeptide whose ATP-dependent conjugation to target proteins represents an initial obligatory step in their degradation. The mouse cell-cycle mutant cell-line, ts85 122, 231, fails to conjugate ubiquitin at the non-permissive temperature [24], due to thermolability of its ubiquitin-activating enzyme E l [25]. One of these studies [24] has actually suggested that the degradation of the bul...

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Section: Discussionmentioning

confidence: 79%

Degradation of ornithine decarboxylase in mammalian cells is ATP dependent but ubiquitin independent

Rosenberg-Hasson

Bercovich

Ciechanover

et al. 1989

European Journal of Biochemistry

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“…Experimental manipulations of the levels of polyamines within cells result in rapid changes in ODC activity, but such treatments have no discernible effect on the amount of ODC mRNA (5,12,16,18,(27)(28)(29)35). It has been reported that the rate of synthesis of the enzyme, measured by metabolic labeling with radioactive amino acids, is reduced when intracellular polyamines are augmented, and the opposite result is found when cells are depleted of polyamines (11,12,16,20,21,25,27).…”

mentioning

confidence: 99%

Polyamine-mediated regulation of mouse ornithine decarboxylase is posttranslational.

Wetters¹,

Macrae²,

Brabant³

et al. 1989

Mol. Cell. Biol.

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“…translation (Dirks et al, 1986;Sertich & Pegg, 1987;Persson et al, 1986;Kahana & Nathans, 1985) and/or by post-translational mechanisms (Heller et al, 1976;McCann et al, 1979;Murakami & Hayashi, 1986). As a further test of this possibility, it would be interesting to determine whether 6-spermyne negatively regulates translation of AdoMetDC mRNA, but not ODC mRNA, in the reticulocyte-lysate translation system in vitro (Kameji & Pegg, 1987).…”

mentioning

confidence: 99%

Selective regulation of S-adenosylmethionine decarboxylase activity by the spermine analogue 6-spermyne

Porter

McManis

Lee

et al. 1988

Biochemical Journal

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Polyamine-biosynthesis activity is known to be negatively regulated by intracellular polyamine pools. Accordingly, treatment of cultured L1210 cells with 10 microM-spermine rapidly and significantly lowered ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities in a sequential manner. By contrast, treatment for 48 h with 10 microM of the unsaturated spermine analogue 6-spermyne lowered AdoMetDC activity, but not ODC activity. An initial decrease in ODC activity at 2 h was attributed to a transient increase in free intracellular spermidine and spermine brought about through their displacement by the analogue. Thereafter, ODC activity recovered steadily to control values as 6-spermyne pools increased and spermidine and spermine pools decreased owing to analogue suppression of AdoMetDC activity. The apparent ability of 6-spermyne to regulate AdoMetDC, but not ODC, activity suggests an interesting structure-function correlation and demonstrates that the typical co-regulation of these enzyme activities can be dissociated. This, in turn, may reflect the existence of independent regulatory binding sites for the two enzymes.

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Posttranscriptional regulation of ornithine decarboxylase activity

Cited by 62 publications

References 30 publications

Degradation of ornithine decarboxylase in mammalian cells is ATP dependent but ubiquitin independent

Degradation of ornithine decarboxylase in mammalian cells is ATP dependent but ubiquitin independent

Polyamine-mediated regulation of mouse ornithine decarboxylase is posttranslational.

Selective regulation of S-adenosylmethionine decarboxylase activity by the spermine analogue 6-spermyne

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