title: Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell.
abstract: 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.
authors.affiliation: Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Leonor
authors.initials: L
authors.lastname: Miller-Fleming
authors.affiliation: Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Viridiana
authors.initials: V
authors.lastname: Olin-Sandoval
authors.affiliation: Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Campbell
authors.affiliation: Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom; The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Electronic address: mr559@cam.ac.uk.
authors.forename: Markus
authors.initials: M
authors.lastname: Ralser
mesh_terms: D000375:Aging; D000818:Animals; D053898:Biosynthetic Pathways; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D011073:Polyamines / Q000032:analysis / Q000378:metabolism*
chemical_list: D011073:Polyamines; D009955:Ornithine Decarboxylase
keywords: Cancer; Hypusine; Neurodegenerative diseases; Proliferation; Stress response