Regulation of mammalian S-Adenosylmethionine decarboxylase

Pegg, Anthony E.; Kameji, Takaaki; Shirahata, Akira; Stanley, Bruce A.; Madhubala, Rentala; Pajunen, Antti

doi:10.1016/0065-2571(88)90008-8

Cited by 39 publications

(35 citation statements)

References 22 publications

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“…Like other rate-limiting enzymes, SAMDC has a short half-life, its basal activity is low, and it is rapidly induced by different stimuli (64,66,67). Furthermore, SAMDC is synthesized as an inactive proenzyme that, in response to different stimuli, undergoes an intramolecular cleavage reaction to form the active enzyme (46,64,66). Thus, it is possible that one or more of the processes that affect the activity of SAMDC could be modulated upon interaction with HtpB.…”

Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

“…6a) could be interpreted as meaning that SAMDC activity, rather than increased concentrations of spermidine and spermine, is necessary for the optimal growth of L. pneumophila. This is made all the more plausible by the knowledge that inhibition of ornithine decarboxylase by DFMO is known to increase SAMDC activity (66). However, DFMO might simply have a late effect on the polyamine pool of host cells due to its slow uptake (78), its inability to effectively reduce spermine levels in treated cells (32), or the expected long period required to exhaust the levels of putrescine, and consequently spermidine, in host cells.…”

Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

“…SAMDC is a rate-limiting enzyme key in the biosynthesis of polyamines, which is tightly regulated in eukaryotic cells (67). Like other rate-limiting enzymes, SAMDC has a short half-life, its basal activity is low, and it is rapidly induced by different stimuli (64,66,67). Furthermore, SAMDC is synthesized as an inactive proenzyme that, in response to different stimuli, undergoes an intramolecular cleavage reaction to form the active enzyme (46,64,66).…”

Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

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Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

et al. 2011

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The Gram-negative intracellular pathogen Legionella pneumophila replicates in a membrane-bound compartment known as the Legionella-containing vacuole (LCV), into which it abundantly releases its chaperonin, HtpB. To determine whether HtpB remains within the LCV or reaches the host cell cytoplasm, we infected U937 human macrophages and CHO cells with L. pneumophila expressing a translocation reporter consisting of the Bordetella pertussis adenylate cyclase fused to HtpB. These infections led to increased cyclic AMP levels, suggesting that HtpB reaches the host cell cytoplasm. To identify potential functions of cytoplasmic HtpB, we expressed it in the yeast Saccharomyces cerevisiae, where HtpB induced pseudohyphal growth. A yeast-twohybrid screen showed that HtpB interacted with S-adenosylmethionine decarboxylase (SAMDC), an essential yeast enzyme (encoded by SPE2) that is required for polyamine biosynthesis. Increasing the copy number of SPE2 induced pseudohyphal growth in S. cerevisiae; thus, we speculated that (i) HtpB induces pseudohyphal growth by activating polyamine synthesis and (ii) L. pneumophila may require exogenous polyamines for growth. A pharmacological inhibitor of SAMDC significantly reduced L. pneumophila replication in L929 mouse cells and U937 macrophages, whereas exogenously added polyamines moderately favored intracellular growth, confirming that polyamines and host SAMDC activity promote L. pneumophila proliferation. Bioinformatic analysis revealed that most known enzymes required for polyamine biosynthesis in bacteria (including SAMDC) are absent in L. pneumophila, further suggesting a need for exogenous polyamines. We hypothesize that HtpB may function to ensure a supply of polyamines in host cells, which are required for the optimal intracellular growth of L. pneumophila.Chaperonins constitute a family of highly conserved proteins found in all prokaryotic and eukaryotic organisms (34). Their primary role is to facilitate the folding of nascent and stressdenatured proteins into their functional native states in an ATP-dependent manner (54). Group I chaperonins, referred to as Hsp60, Cpn60, or GroEL, are prokaryotic proteins found in bacteria and in eukaryotic organelles such as mitochondria and chloroplasts (34). Group II chaperonins, also known as CCT or TCP-1, are found in the eukaryotic cytosol and in the archaea (34). Structural and functional studies of Escherichia coli GroEL have established the role of group I chaperonins as intracellular mediators of protein folding (7, 94). GroEL is an essential protein in E. coli (23) whose intracellular level increases substantially in response to defined stressful stimuli (55, 85). The protein-folding paradigm of group I chaperonins has changed with accumulating reports of surface-and membrane-associated chaperonins that perform other diverse functions. For instance, the extracytoplasmically localized chaperonins of Haemophilus ducreyi (25), Helicobacter pylori (9, 92), Borrelia burgdorferi (77), and Clostridium difficile (37) have been implica...

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Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

Section: Htpb Reaches the Cytosol Of L Pneumophila-infected Cellsmentioning

confidence: 99%

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Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

et al. 2011

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“…Like other rate-limiting enzymes, SAMDC has a short halflife, its basal activity is low, and it is rapidly induced by different stimuli [28][29][30]. Additionally, SAMDC is synthesized as an inactive proenzyme that in response to different stimuli undergoes an intramolecular cleavage reaction to form the active enzyme [28,31,32]. Thus, having said that HtpB is essentially a chaperonin that is important in protecting proteins from denaturation, it is possible that one or more of the processes that infl uence the function of SAMDC could be enhanced upon interaction with HtpB.…”

Section: Discussionmentioning

confidence: 99%

A yeast two-hybrid screen reveals a strong interaction between the Legionella chaperonin Hsp60 and the host cell small heat shock protein Hsp10

Nasrallah

2015

Acta Microbiologica et Immunologica Hungarica

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L. pneumophila is an intracellular bacterium that replicates inside a membrane-bound vacuole called Legionella-containing vacuole (LCV), where it plentifully liberates its HtpB chaperonin. From LCV, HtpB reaches the host cell cytoplasm, where it interacts with SAMDC, a cytoplasmic protein required for synthesis of host polyamines that are important for intracellular growth of L. pneumophila. Additionally, cytoplasmic expression of HtpB in S. cerevisiae induces pseudohyphal growth, and in mammalian cells recruits mitochondria to LCV, and modifi es actin microfi laments organization. This led us to hypothesize here that HtpB recruits a protein(s) from eukaryotic cells that is involved in the emergence of the aforementioned phenotypes. To identify this protein, a commercially available HeLa cDNA library was screened using a yeast two-hybrid system. Approximately 5×10 6 yeast clones carrying HeLa cDNA library plasmid were screened. Twenty-one positive clones were identifi ed. DNA sequence analysis revealed that all of these positive clones encoded the mammalian small heat shock protein Hsp10. Based on the fact that chaperonions are required to interact with co-chaperonins to function properly in protein folding, we believe that HtpB recruits the host cell Hsp10 to appropriately interact with SAMDC and to induce the multifunction phenotypes deemed important in L. pneumophila pathogenesis.

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“…The activity of AdoMetDC is regulated negatively by spermidine and spermine [3], and polyamine depletion leads to an increase in the amount of AdoMetDC protein, caused by both a decreased rate of degradation and an increased rate of synthesis. The increased synthesis has been shown to be partly due to an enhanced translational efficiency [4]. However, much less is known about AdoMetDC regulation than about ornithine decarboxylase (OmDC), another key enzyme in polyamine biosynthesis.…”

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confidence: 99%

Overproduction of S‐adenosylmethionine decarboxylase in ethylglyoxal‐bis(guanylhydrazone)‐resistant mouse FM3A cells

Suzuki

Sadakat

Kashiwagi

et al. 1993

European Journal of Biochemistry

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A variant cell line, termed SAM-1, which overproduced S-adenosylmethionine decarboxylase inhibitor of AdoMetDC, necessary to inhibit cell growth was also five-times more in SAM-1 cells than in control cells. However, the following were the same in both SAM-1 and control cells; the amount of genomic DNA for AdoMetDC, the size and nucleotide sequence of 5' untranslated region of AdoMetDC mRNA, the deduced amino acid sequence (334 residues) from the nucleotide sequence of AdoMetDC cDNA and the degradation rate (t,,2 = about 4 h) of AdoMetDC. In addition, AdoMetDC mRNA in control cells was slightly more stable than that in SAM-1 cells. The results indicate that the overproduction of AdoMetDC in SAM-1 cells was caused by the increase of AdoMetDC mRNA. The variant cell line is convenient for studying the regulation of AdoMetDC and the physiological function of polyamines.S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in polyamine biosynthesis. Its product, decarboxylated S-adenosylmethionine, serves as an amino propyl donor in spermidine and spennine synthesis [l, 21. The activity of AdoMetDC is regulated negatively by spermidine and spermine [3], and polyamine depletion leads to an increase in the amount of AdoMetDC protein, caused by both a decreased rate of degradation and an increased rate of synthesis. The increased synthesis has been shown to be partly due to an enhanced translational efficiency [4]. However, much less is known about AdoMetDC regulation than about ornithine decarboxylase (OmDC), another key enzyme in polyamine biosynthesis. As one of the means of studying of Correspondence to K. Igarashi, Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, Japan, 263Far: +81 43 255 1574.

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Regulation of mammalian S-Adenosylmethionine decarboxylase

Cited by 39 publications

References 22 publications

Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

Legionella pneumophilaRequires Polyamines for Optimal Intracellular Growth

A yeast two-hybrid screen reveals a strong interaction between the Legionella chaperonin Hsp60 and the host cell small heat shock protein Hsp10

Overproduction of S‐adenosylmethionine decarboxylase in ethylglyoxal‐bis(guanylhydrazone)‐resistant mouse FM3A cells

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