Extremely rapid turnover of S‐adenosylmethionine decarboxylase in <i>Crithidia fasciculata</i>

Nasizadeh, Sima; Persson, Lo

doi:10.1016/s0014-5793(03)00986-4

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…Similar to ODC, AdoMetDC half-life is short (less than 1 hour), and in extreme cases like in Crithidia fasciculata, the turnover occurs in 3 minutes [73]. AdoMetDC turnover accelerates when concentrations of Spd and Spm are high [67].…”

Section: Polyamines and S-adenosylmethionine Decarboxylase (Adometdc)mentioning

confidence: 99%

Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell

Miller-Fleming

Olín-Sandoval

Campbell

et al. 2015

Journal of Molecular Biology

543

522

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The polyamines (PAs) spermidine, spermine, putrescine and cadaverine are an essential class of metabolites found throughout all kingdoms of life. In this comprehensive review, we discuss their metabolism, their various intracellular functions and their unusual and conserved regulatory features. These include the regulation of translation via upstream open reading frames, the over-reading of stop codons via ribosomal frameshifting, the existence of an antizyme and an antizyme inhibitor, ubiquitin-independent proteasomal degradation, a complex bi-directional membrane transport system and a unique posttranslational modification-hypusination-that is believed to occur on a single protein only (eIF-5A). Many of these features are broadly conserved indicating that PA metabolism is both concentration critical and evolutionary ancient. When PA metabolism is disrupted, a plethora of cellular processes are affected, including transcription, translation, gene expression regulation, autophagy and stress resistance. As a result, the role of PAs has been associated with cell growth, aging, memory performance, neurodegenerative diseases, metabolic disorders and cancer. Despite comprehensive studies addressing PAs, a unifying concept to interpret their molecular role is missing. The precise biochemical function of polyamines is thus one of the remaining mysteries of molecular cell biology.

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Section: Polyamines and S-adenosylmethionine Decarboxylase (Adometdc)mentioning

confidence: 99%

Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell

Miller-Fleming

Olín-Sandoval

Campbell

et al. 2015

Journal of Molecular Biology

543

522

View full text Add to dashboard Cite

show abstract

“…It has been reported that the half-life of AdoMetDC is inversely related to the cellular content of spermidine and spermine (9 -11), so that when the levels of polyamines are high, increased degradation of AdoMetDC serves as another important control mechanism in maintaining AdoMetDC activity and therefore polyamine levels (3,5). The half-life of AdoMetDC is usually 1-3 h in most cell lines and tissues (13)(14)(15)(16)(17)(18), although an AdoMetDC half-life of only 3 min has recently been reported for the parasite Crithidia fasciculata (19). In vivo the rapid degradation of AdoMetDC is inhibited by the binding of activity inhibitors such as methylglyoxal bis(guanyl)hydrazone, aminoguanidine, S-methyl-5Ј-methylthioadenosine, or 4-amidinoindan-1-one 2Ј-amidinohydrazone (5,14,20,21).…”

mentioning

confidence: 99%

S-Adenosylmethionine Decarboxylase Degradation by the 26 S Proteasome Is Accelerated by Substrate-mediated Transamination

Yerlikaya

Stanley

2004

Journal of Biological Chemistry

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The short-lived enzyme S-adenosylmethionine decarboxylase uses a covalently bound pyruvoyl cofactor to catalyze the formation of decarboxylated S-adenosylmethionine, which then donates an aminopropyl group for polyamine biosynthesis. Here we demonstrate that S-adenosylmethionine decarboxylase is ubiquitinated and degraded by the 26 S proteasome in vivo, a process that is accelerated by inactivation of S-adenosylmethionine decarboxylase by substrate-mediated transamination of its pyruvoyl cofactor. Proteasome inhibition in COS-7 cells prevents the degradation of S-adenosylmethionine decarboxylase antigen; however, even brief inhibition of the 26 S proteasome caused substantial losses of S-adenosylmethionine decarboxylase activity despite accumulation of S-adenosylmethionine decarboxylase antigen. Levels of the enzyme's substrate (S-adenosylmethionine) increased rapidly after 26 S proteasome inhibition, and this increase in substrate level is consistent with the observed loss of activity arising from an increased rate of inactivation by substrate-mediated transamination. Evidence is also presented that this substrate-mediated transamination accelerates normal degradation of S-adenosylmethionine decarboxylase, as the rate of degradation of the enzyme was increased in the presence of AbeAdo (5 -([(Z)-4-amino-2-butenyl]methylamino]-5 -deoxyadenosine) (a substrate analogue that transaminates the enzyme); conversely, when the intracellular substrate level was reduced by methionine deprivation, the rate of degradation of the enzyme was decreased. Ubiquitination of S-adenosylmethionine decarboxylase is demonstrated by isolation of His-tagged AdoMetDC (S-adenosylmethionine decarboxylase) from COS-7 cells co-transfected with hemagglutinin-tagged ubiquitin and showing bands that were immunoreactive to both anti-AdoMetDC antibody and anti-hemagglutinin antibody. This is the first study to demonstrate that AdoMetDC is ubiquitinated and degraded by the 26 S proteasome, and substrate-mediated acceleration of degradation is a unique finding.

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“…No reports exist describing the half-life of T. cruzi AdoMetDC. Analysis of AdoMetDC in C. fasciculata showed that the enzyme has a very fast turnover in the parasite, with a halflife as short as 3 min, which appears to be the shortest half-life ever recorded for a eukaryotic AdoMetDC [44]. As for the mammalian enzyme, putrescine has a direct stimulatory effect on AdoMetDCs from T. brucei [45], T. cruzi [11,46] and C. fasciculata [44].…”

Section: Adometdcmentioning

confidence: 91%

Ornithine decarboxylase and S-adenosylmethionine decarboxylase in trypanosomatids

Persson

2007

Biochemical Society Transactions

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The production of polyamines has been shown to be an effective target for a drug against the West African form of sleeping sickness caused by Trypanosoma brucei gambiense. T. brucei belongs to the group of protozoan parasites classed as trypanosomatids. Parasitic species of this group are the causative agents of various tropical diseases besides African sleeping sickness, e.g. Chagas' disease (Trypanosoma cruzi), cutaneous (Lesihmania spp.) and visceral (Leishmania donovani) leishmaniasis. The metabolism of polyamines in the parasites is a potential target for the development of new drugs for treatment of these diseases. The key steps in polyamine synthesis are catalysed by ODC (ornithine decarboxylase) and AdoMetDC (S-adenosylmethionine decarboxylase). In the present paper, some of the available information on ODC and AdoMetDC in trypanosomatids will be described and discussed.

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Extremely rapid turnover of S‐adenosylmethionine decarboxylase in Crithidia fasciculata

Cited by 5 publications

References 33 publications

Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell

Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell

S-Adenosylmethionine Decarboxylase Degradation by the 26 S Proteasome Is Accelerated by Substrate-mediated Transamination

Ornithine decarboxylase and S-adenosylmethionine decarboxylase in trypanosomatids

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