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

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Miller-Fleming, Leonor 
Olin-Sandoval, Viridiana 
Campbell, Kate 


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.



Cancer, Hypusine, Neurodegenerative diseases, Proliferation, Stress response, Aging, Animals, Biosynthetic Pathways, Cell Proliferation, Gene Expression Regulation, Humans, Neoplasms, Neurodegenerative Diseases, Ornithine Decarboxylase, Polyamines

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J Mol Biol

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Elsevier BV
European Research Council (260809)
We thank the Wellcome Trust (RG 093735/Z/10/Z to MR), the ERC (Starting grant 260809 to MR) and the Consejo Nacional de Ciencia y Tecnologia (CONACyT) Mexico postdoctoral fellowship 232510 to VO-S. Markus Ralser is a Wellcome-Trust Research career development and Wellcome-Beit prize fellow.