A perspective of polyamine metabolism

Wallace, Heather M.; Fraser, Alison V.; Hughes, Alun D.

doi:10.1042/bj20031327

Cited by 842 publications

(730 citation statements)

References 190 publications

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“…For example, a circadian change of polyamine levels is observed during cell cycle [48] and the translation initiation factor eIF5A's biochemical activity on cellular proliferation is tightly linked to cellular polyamine homeostasis, especially to spermidine modification [49]. The observation on ODC knockout mouse suggests that putrescine plays a key role in cell growth [50].…”

Section: Roles Of Plant Polyaminesmentioning

confidence: 99%

BUD2, encoding an S-adenosylmethionine decarboxylase, is required for Arabidopsis growth and development

et al. 2006

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Polyamines are implicated in regulating various developmental processes in plants, but their exact roles and how they govern these processes still remain elusive. We report here an Arabidopsis bushy and dwarf mutant, bud2, which results from the complete deletion of one member of the small gene family that encodes S-adenosylmethionine decarboxylases (SAMDCs) necessary for the formation of the indispensable intermediate in the polyamine biosynthetic pathway. The bud2 plant has enlarged vascular systems in inflorescences, roots, and petioles, and an altered homeostasis of polyamines. The double mutant of bud2 and samdc1, a knockdown mutant of another SAMDC member, is embryo lethal, demonstrating that SAMDCs are essential for plant embryogenesis. Our results suggest that polyamines are required for the normal growth and development of higher plants.Cell Research (2006) IntroductionPolyamines, including diamine putrescine, triamine spermidine and tetraamine spermine, are aliphatic nitrogen compounds distributed widely from bacteria to higher plants [1,2] and have been implicated to play important roles in growth and development [3]. At the cellular level, polyamines are organic cations, interacting with the macromolecules that possess anionic groups such as DNA, RNA, lipids and proteins, thereby influencing DNA conformation, gene expression and protein synthesis, and modulating enzyme activity. In higher plants, polyamines are able to affect membrane fluidity by binding to phospholipids in membrane [4] and mediate biotic and abiotic stress responses, such as pathogen infection, osmotic stress, potassium deficiency and wounding [5][6][7][8][9]. Previous observations revealed that polyamines may be involved in a variety of plant developmental processes, such as cell division, root initiation, somatic embryogenesis, xylogenesis, flower development, fruit ripening and senescence [3]. Recent studies have indicated that polyamines also affect the formation of plant architecture, such as internode elongation [10,11], root branching [12] and shoot apical dominance [13].The plant polyamine biosynthetic pathway is relatively simple [14]. Putrescine is derived either from ornithine catalyzed by ornithine decarboxylase (ODC) or from arginine through several steps catalyzed by arginine decarboxylase (ADC), agmatine iminohydrolase and N-carbamoylputrescine amidohydrolase. Spermidine and spermine are synthesized from putrescine through spermidine and spermine synthases (SPDS and SPMS) from the donor of decarboxylated S-adenosylmethionine (dcSAM), which is produced from S-adenosylmethionine (SAM) by the action of S-adenosylmethionine decarboxylase (SAMDC).Although application of inhibitors is very useful in studying the polyamine biosynthetic pathway and in ex- [11,[19][20][21][22][23][24]. However, no mutant defective in SAMDC has been reported yet, although SAMDC cDNAs were cloned and their transgenic plants have been generated [25][26][27][28][29]. In this paper, we report the isolation and characterization of an Arabidopsis...

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Section: Roles Of Plant Polyaminesmentioning

confidence: 99%

BUD2, encoding an S-adenosylmethionine decarboxylase, is required for Arabidopsis growth and development

et al. 2006

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“…Cells were seeded 2-3 h before treatment with 5 mM DFMO and/or 10 mM Proposed interplay between polyamines and cell cycle regulatory proteins in MYCN-amplified NB cells. Polyamines play a key role in cell cycle regulation (Wallace et al, 2003), but proteins which are directly regulated by polyamines are still poorly defined.…”

Section: Cell Lines and Treatment Of Cultured Cellsmentioning

confidence: 99%

Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells

et al. 2005

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Alpha-difluoromethylornithine (DFMO) inhibits the protooncogene ornithine decarboxylase (ODC) and is known to induce cell cycle arrest. However, the effect of DFMO on human neuroblastoma (NB) cells and the exact mechanism of DFMO-induced cell death are largely unknown. Treatment with DFMO in combination with SAM486A, an S-adenosylmethionine decarboxylase (AdoMetDC) inhibitor, has been shown to enhance polyamine pool depletion. Therefore, we analysed the mechanism of action of DFMO and/or SAM486A in two established MYCN-amplified human NB cell lines. DFMO and SAM486A caused rapid cell growth inhibition, polyamine depletion, and G 1 cell cycle arrest without apoptosis in cell lines LAN-1 and NMB-7. These effects were enhanced with combined inhibitors and largely prevented by cotreatment with exogenous polyamines. The G 1 cell cycle arrest was concomitant with an increase in cyclin-dependent kinase inhibitor p27 Kip1 . In a similar fashion, DFMO and DFMO/SAM486A inhibited the phosphorylation of the G 1 /S transition-regulating retinoblastoma protein Rb at residues Ser795 and Ser807/811. Moreover, we observed a dramatic decrease in MYCN protein levels. Overexpression of MYCN induces an aggressive NB phenotype with malignant behavior. We show for the first time that DFMO and SAM486A induce G 1 cell cycle arrest in NB cells through p27 Kip1 and Rb hypophosphorylation.

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“…Intracellularly, polyamines are small, multivalent, positively charged molecules which are highly regulated during the cell cycle (Wallace et al 2003). They bind non-specifically to DNA and modify topology, as shown in our recent study (Shao et al 2012), in which we in particular considered the effects of spermidine (three positive charges) and spermine (four positive charges).…”

Section: Dna Under Torsion Twists and Then Supercoilsmentioning

confidence: 94%

Supercoiling biases the formation of loops involved in gene regulation

Finzi

Dunlap

2016

Biophys Rev

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The function of DNA as a repository of genetic information is well-known. The post-genomic effort is to understand how this information-containing filament is chaperoned to manage its compaction and topological states. Indeed, the activities of enzymes that transcribe, replicate, or repair DNA are regulated to a large degree by access. Proteins that act at a distance along the filament by binding at one site and contacting another site, perhaps as part of a bigger complex, create loops that constitute topological domains and influence regulation. DNA loops and plectonemes are not necessarily spontaneous, especially large loops under tension for which high energy is required to bring their ends together, or small loops that require accessory proteins to facilitate DNA bending. However, the torsion in stiff filaments such as DNA dramatically modulates the topology, driving it from extended and genetically accessible to more looped and compact, genetically secured forms. Furthermore, there are accessory factors that bias the response of the DNA filament to supercoiling. For example, small molecules like polyamines, which neutralize the negative charge repulsions along the phosphate backbone, enhance flexibility and promote writhe over twist in response to torsion. Such increased flexibility likely pushes the topological equilibrium from twist toward writhe at tensions thought to exist in vivo. A predictable corollary is that stiffening DNA antagonizes looping and bending. Certain sequences are known to be more or less flexible or to exhibit curvature, and this may affect interactions with binding proteins. In vivo all of these factors operate simultaneously on DNA that is generally negatively supercoiled to some degree. Therefore, in order to better understand gene regulation that involves protein-mediated DNA loops, it is critical to understand the thermodynamics and kinetics of looping in DNA that is under tension, negatively supercoiled, and perhaps exposed to molecules that alter elasticity. Recent experiments quantitatively reveal how much negatively supercoiling DNA lowers the free energy of looping, possibly biasing the operation of genetic switches.

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A perspective of polyamine metabolism

Cited by 842 publications

References 190 publications

BUD2, encoding an S-adenosylmethionine decarboxylase, is required for Arabidopsis growth and development

BUD2, encoding an S-adenosylmethionine decarboxylase, is required for Arabidopsis growth and development

Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells

Supercoiling biases the formation of loops involved in gene regulation

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