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dc.contributor.authorLane, Darius JR
dc.contributor.authorBae, Dong-Hun
dc.contributor.authorSiafakas, Aritee R
dc.contributor.authorRahmanto, Yohan Suryo
dc.contributor.authorAl-Akra, Lina
dc.contributor.authorJansson, Patric J
dc.contributor.authorCasero, Robert A
dc.contributor.authorRichardson, Des R
dc.date.accessioned2021-04-29T23:50:09Z
dc.date.available2021-04-29T23:50:09Z
dc.date.issued2018
dc.identifier.issn0925-4439
dc.identifier.doi10.1016/j.bbadis.2018.05.007
dc.identifier.urihttp://hdl.handle.net/10072/404039
dc.description.abstractMany biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins. Seven of these were regulated in a conserved manner by iron-depletion across different cell-types, with four proteins being down-regulated (i.e., acireductone dioxygenase 1 [ADI1], methionine adenosyltransferase 2α [MAT2α], Antizyme and polyamine oxidase [PAOX]) and three proteins being up-regulated (i.e., S-adenosyl methionine decarboxylase [AMD1], Antizyme inhibitor 1 [AZIN1] and spermidine/spermine-N -acetyltransferase 1 [SAT1]). Depletion of iron also markedly decreased polyamine pools (i.e., spermidine and/or spermine, but not putrescine). Accordingly, iron-depletion also decreased S-adenosylmethionine that is essential for spermidine/spermine biosynthesis. Iron-depletion additionally reduced H-spermidine uptake in direct agreement with the lowered levels of the polyamine importer, SLC22A16. Regarding mechanism, the “reprogramming” of polyamine metabolism by iron-depletion is consistent with the down-regulation of ADI1 and MAT2α and the up-regulation of SAT1. Moreover, changes in ADI1 (biosynthetic) and SAT1 (catabolic) partially depended on the iron-regulated changes in c-Myc and/or p53. The ability of iron chelators to inhibit proliferation was rescuable by putrescine and spermidine, and under some conditions by spermine. Collectively, iron and polyamine metabolism are intimately coupled, which has significant ramifications for understanding the integrated role of iron and polyamine metabolism in proliferation. 1 3
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherELSEVIER
dc.relation.ispartofpagefrom2793
dc.relation.ispartofpageto2813
dc.relation.ispartofissue9
dc.relation.ispartofjournalBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
dc.relation.ispartofvolume1864
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.subject.fieldofresearchcode3202
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiochemistry & Molecular Biology
dc.subject.keywordsBiophysics
dc.subject.keywordsCell Biology
dc.titleCoupling of the polyamine and iron metabolism pathways in the regulation of proliferation: Mechanistic links to alterations in key polyamine biosynthetic and catabolic enzymes
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationLane, DJR; Bae, D-H; Siafakas, AR; Rahmanto, YS; Al-Akra, L; Jansson, PJ; Casero, RA; Richardson, DR, Coupling of the polyamine and iron metabolism pathways in the regulation of proliferation: Mechanistic links to alterations in key polyamine biosynthetic and catabolic enzymes, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2018, 1864 (9), pp. 2793-2813
dcterms.dateAccepted2018-05-12
dcterms.licensehttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2021-04-29T23:42:40Z
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2018 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorRichardson, Des R.


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