論文 - 植村 武史
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Correlation of polyamines, acrolein-conjugated lysine and polyamine metabolic enzyme levels with age in human liver. 査読あり
Uemura Takeshi, Akasaka Yoshihisa, Ikegaya Hiroshi
Heliyon 6 ( 9 ) e05031 - e05031 2020年09月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
The polyamines spermidine, spermine and putrescine are essential for normal cellular functions. The contents of polyamines in tissue decreased in aged mice compared to young mice. In this study, the polyamine contents and their metabolic byproduct acrolein-conjugated lysine (N (ε)-(3-formyl-3,4-dehydropiperidino)-lysine, FDP-Lys) in human liver tissue were measured and analyzed the correlation with age of the subjects. The putrescine and FDP-Lys levels were significantly increased with age. On the other hand, spermine level was decreased with age. Spermidine did not significantly correlate with age. The relative amount of spermine oxidase (SMOX) significantly correlated with the age of subjects whereas ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase (AMD1) significantly reduced by the age. Our results suggested that an increase in oxidation and reduction in polyamine synthesis may cause the change of polyamine profile in the elderly.
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A search for acrolein scavengers among food components 査読あり
Uemura T, Uchida M, Nakamura M, Shimekake M, Sakamoto A, Terui Y, Higashi K, Ishii I, Kashiwagi K, Igarashi K.
Amino Acids 2023年02月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
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Nα-(5-Fluoro-2,4-dinitrophenyl)-L-leucinamide-derivatized LC/MS/MS Analysis of Amino Acid Enantiomers in HepG2 Cells 査読あり
Takano Y, Takahashi M, Kobayashi M, Uemura T, Furuchi T.
Chromatography 42 ( 3 ) 143 - 149 2021年
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Structural change and degradation of cytoskeleton due to the acrolein conjugation with vimentin and actin during brain infarction. 査読あり
Uemura Takeshi, Suzuki Takehiro, Ko Kenta, Nakamura Mizuho, Dohmae Naoshi, Sakamoto Akihiko, Terui Yusuke, Toida Toshihiko, Kashiwagi Keiko, Igarashi Kazuei
Cytoskeleton (Hoboken) 77 ( 10 ) 414 - 421 2020年10月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
We have found recently that dendritic spine extension is inhibited through acrolein conjugation with α- and β-tubulin proteins during brain infarction. In this current study, we looked for other acrolein-conjugated proteins in the 100,000g precipitate fraction, to clarify how cytoskeleton structure is modified by acrolein. Acrolein-conjugated proteins were sought from acrolein-treated mouse FM3A and Neuro2a cells and from tissues isolated from mouse brain infarction. It was found that vimentin was conjugated with acrolein, and the conjugated amino acid residue was Cys328, which is the only Cys residue in vimentin. It was also found that Cys207, 257, 285, and Lys118 in actin, another cytoskeleton protein, were conjugated with acrolein. The structure and localization of vimentin and actin filaments were changed greatly in infarct brain in photochemically induced thrombosis model mice and in acrolein-treated Neuro2a cells. In addition, degradation of cytoskeleton proteins was accelerated in the order vimentin > tubulin > actin in mouse brain infarction. These findings indicate that a dysfunction of the cytoskeleton by acrolein is strongly involved in the tissue damage during brain infarction, together with the apoptosis caused by glyceraldehyde-3-phosphate dehydrogenase and protein degradation by matrix metalloproteinase-9.
DOI： 10.1002/cm.21638
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Urinary Amino Acid-Conjugated Acrolein and Taurine as New Biomarkers for Detection of Dementia 査読あり
Yoshida M, Uemura T, Mizoi M, Waragai M, Sakamoto A, Terui Y, Kashiwagi K, Igarashi K.
J Alzheimers Dis. 2023年01月
担当区分：第二著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
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Polyamine analysis of acidophiles, alkaliphiles, halophiles and thermophiles belonging to the bacterial phyla Actinobacteria, Aquificae, Bacterioidetes, Cyanobacteria, Desulfobacterota, Firmicutes, Tenericutes, and Thermotogae – Polyamine catalogue of bacterial and archaeal extremophiles – (XII) 査読あり
Koei Hamana, Hidenori Hayashi, Takemitsu Furuchi, Takeshi Uemura, Masaru Niitsu, Takashi Itoh, Mitsuo Sakamoto, and Moriya Okuma
Journal of Japanese Society for Extremophiles 2022年
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Polyamines produced by an extreme thermophile are essential for cell growth at high temperature 査読あり
Akihiko Sakamoto, Masatada Tamakoshi, Toshiyuki Moriya, Tairo Oshima, Koichi Takao, Yoshiaki Sugita, Takemitsu Furuchi, Masaru Niitsu, Takeshi Uemura, Kazuei Igarashi, Keiko Kashiwagi, Yusuke Terui.
Journal of Biochemistry 172 ( 2 ) 109 - 115 2022年
記述言語：英語 掲載種別：研究論文（学術雑誌）
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The Polyamine Regulator AMD1 Upregulates Spermine Levels to Drive Epidermal Differentiation. 招待あり 査読あり 国際共著
Rahim Anisa B, Lim Hui Kheng, Tan Christina Yan Ru, Jia Li, Leo Vonny Ivon, Uemura Takeshi, Hardman-Smart Jonathan, Common John E A, Lim Thiam Chye, Bellanger Sophie, Paus Ralf, Igarashi Kazuei, Yang Henry, Vardy Leah A
J Invest Dermatol 141 ( 9 ) 2178 - 2188.e6 2021年09月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Maintaining tissue homeostasis depends on a balance between cell proliferation, differentiation, and apoptosis. Within the epidermis, the levels of the polyamines putrescine, spermidine, and spermine are altered in many different skin conditions, yet their role in epidermal tissue homeostasis is poorly understood. We identify the polyamine regulator, Adenosylmethionine decarboxylase 1 (AMD1), as a crucial regulator of keratinocyte (KC) differentiation. AMD1 protein is upregulated on differentiation and is highly expressed in the suprabasal layers of the human epidermis. During KC differentiation, elevated AMD1 promotes decreased putrescine and increased spermine levels. Knockdown or inhibition of AMD1 results in reduced spermine levels and inhibition of KC differentiation. Supplementing AMD1-knockdown KCs with exogenous spermidine or spermine rescued aberrant differentiation. We show that the polyamine shift is critical for the regulation of key transcription factors and signaling proteins that drive KC differentiation, including KLF4 and ZNF750. These findings show that human KCs use controlled changes in polyamine levels to modulate gene expression to drive cellular behavior changes. Modulation of polyamine levels during epidermal differentiation could impact skin barrier formation or can be used in the treatment of hyperproliferative skin disorders.
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Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study. 査読あり
Soda Kuniyasu, Uemura Takeshi, Sanayama Hidenori, Igarashi Kazuei, Fukui Taro
Med Sci (Basel) 9 ( 2 ) 2021年03月
記述言語：英語 掲載種別：研究論文（学術雑誌）
The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of mice. To test the effects of increased polyamine intake by humans, 30 healthy male volunteers were asked to eat polyamine-rich and ready-to-eat traditional Japanese food (natto) for 12 months. Natto with high polyamine content was used. Another 27 male volunteers were asked not to change their dietary pattern as a control group. The volunteers' age of intervention and control groups ranged from 40 to 69 years (median 48.9 ± 7.9). Two subjects in the control group subsequently dropped out of the study. The estimated increases in spermidine and spermine intakes were 96.63 ± 47.70 and 22.00 ± 9.56 µmol per day in the intervention group, while no changes were observed in the control group. The mean blood spermine level in the intervention group gradually rose to 1.12 ± 0.29 times the pre-intervention level after 12 months, and were significantly higher (p = 0.019) than those in the control group. Blood spermidine did not increase in either group. LFA-1 on monocytes decreased gradually in the intervention group, and there was an inverse association between changes in spermine concentrations relative to spermidine and changes in LFA-1 levels. Contingency table analysis revealed that the odds ratio to decrease LFA-1 by increased polyamine intake was 3.927 (95% CI 1.116-13.715) (p = 0.032) when the effect of acute inflammation was excluded. The results in the study were similar to those of our animal experiments. Since methylation changes of the entire genome are associated with aging-associated pathologies and our previous studies showed that spermine-induced LFA-1 suppression was associated with the inhibition of aberrant gene methylation, the results suggest that dietary polyamine contributes to human health and longevity.
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A Raman algorithm to estimate human age from protein structural variations in autopsy skin samples: a protein biological clock. 査読あり
Miyamori Daisuke, Uemura Takeshi, Zhu Wenliang, Fujikawa Kei, Nakaya Takaaki, Teramukai Satoshi, Pezzotti Giuseppe, Ikegaya Hiroshi
Sci Rep 11 ( 1 ) 5949 - 5949 2021年03月
記述言語：英語 掲載種別：研究論文（学術雑誌）
The recent increase of the number of unidentified cadavers has become a serious problem throughout the world. As a simple and objective method for age estimation, we attempted to utilize Raman spectrometry for forensic identification. Raman spectroscopy is an optical-based vibrational spectroscopic technique that provides detailed information regarding a sample's molecular composition and structures. Building upon our previous proof-of-concept study, we measured the Raman spectra of abdominal skin samples from 132 autopsy cases and the protein-folding intensity ratio, R(PF), defined as the ratio between the Raman signals from a random coil an α-helix. There was a strong negative correlation between age and R(PF) with a Pearson correlation coefficient of r = 0.878. Four models, based on linear (R(PF)), squared (R(PF)(2)), sex, and R(PF) by sex interaction terms, were examined. The results of cross validation suggested that the second model including linear and squared terms was the best model with the lowest root mean squared error (11.3 years of age) and the highest coefficient of determination (0.743). Our results indicate that the there was a high correlation between the age and R(PF) and the Raman biological clock of protein folding can be used as a simple and objective forensic age estimation method for unidentified cadavers.
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Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines. 査読あり
Sakamoto Akihiko, Terui Yusuke, Uemura Takeshi, Igarashi Kazuei, Kashiwagi Keiko
Int J Mol Sci 22 ( 3 ) 2021年01月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Polyamines stimulate the synthesis of specific proteins at the level of translation, and the genes encoding these proteins are termed as the "polyamine modulon". The circadian clock generates daily rhythms in mammalian physiology and behavior. We investigated the role of polyamines in the circadian rhythm using control and polyamine-reduced NIH3T3 cells. The intracellular polyamines exhibited a rhythm with a period of about 24 h. In the polyamine-reduced NIH3T3 cells, the circadian period of circadian clock genes was lengthened and the synthesis of BMAL1 and REV-ERBα was significantly reduced at the translation level. Thus, the mechanism of polyamine stimulation of these protein syntheses was analyzed using NIH3T3 cells transiently transfected with genes encoding enhanced green fluorescent protein (EGFP) fusion mRNA with normal or mutated 5'-untranslated region (5'-UTR) of Bmal1 or Rev-erbα mRNA. It was found that polyamines stimulated BMAL1 and REV-ERBα synthesis through the enhancement of ribosomal shunting during the ribosome shunting within the 5'-UTR of mRNAs. Accordingly, the genes encoding Bmal1 and Rev-erbα were identified as the members of "polyamine modulon", and these two proteins are significantly involved in the circadian rhythm control.
DOI： 10.3390/ijms22031307
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The Polyamine Putrescine Promotes Human Epidermal Melanogenesis. 査読あり
Sridharan Aishwarya, Shi Meng, Leo Vonny Ivon, Subramaniam Nagavidya, Lim Thiam Chye, Uemura Takeshi, Igarashi Kazuei, Tien Guan Steven Thng, Tan Nguan Soon, Vardy Leah A
J Invest Dermatol 140 ( 10 ) 2032 - 2040.e1 2020年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Hyperpigmentary conditions can arise when melanogenesis in the epidermis is misregulated. Understanding the pathways underlying melanogenesis is essential for the development of effective treatments. Here, we report that a group of metabolites called polyamines are important in the control of melanogenesis in human skin. Polyamines are cationic molecules present in all cells and are essential for cellular function. We report that polyamine regulator ODC1 is upregulated in melanocytes from melasma lesional skin. We report that the polyamine putrescine can promote pigmentation in human skin explants and primary normal human epidermal melanocytes through induction of tyrosinase which is rate-limiting for the synthesis of melanin. Putrescine supplementation on normal human epidermal melanocytes results in the activation of polyamine catabolism, which results in increased intracellular H(2)O(2.) Polyamine catabolism is also increased in human skin explants that have been treated with putrescine. We further report that inhibition of polyamine catabolism prevents putrescine-induced promotion of tyrosinase levels and pigmentation in normal human epidermal melanocytes, showing that polyamine catabolism is responsible for the putrescine induction of melanogenesis. Our data showing that putrescine promotes pigmentation has important consequences for hyperpigmented and hypopigmented conditions. Further understanding of how polyamines control epidermal pigmentation could open the door for the development of new therapeutics.
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Development of an ELISA for Measurement of Urinary 3-Hydroxypropyl Mercapturic Acid (3-HPMA), the Marker of Stroke. 査読あり
Sakamoto Akihiko, Uemura Takeshi, Terui Yusuke, Yoshida Madoka, Fukuda Kazumasa, Nakamura Takao, Kashiwagi Keiko, Igarashi Kazuei
Med Sci (Basel) 8 ( 3 ) 2020年08月
記述言語：英語 掲載種別：研究論文（学術雑誌）
We previously observed an inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, through its measurement by liquid chromatography with tandem mass spectrometry (LC-MS/MS). However, the cost of equipment for LC-MS/MS and its maintenance fee is very expensive and a cost-efficient method is required. In this study, we have developed a sensitive enzyme-linked immunosorbent assay (ELISA) system to measure 3-HPMA using a chicken antibody recognizing 3-HPMA-conjugated chicken albumin as antigen. Linearity to measure 3-HPMA was obtained from 0 to 10 μM, indicating that this ELISA system is useful for measurement of urine 3-HPMA. It was confirmed that 3-HPMA in urine of stroke patients decreased significantly compared with that of control subjects using the ELISA system. Using the ELISA kit, it became possible to evaluate the risk of brain stroke by not only plasma but also by urine. These results confirm that shortage of glutathione to detoxify acrolein is one of the major causes of stroke incidence. Our method contributes to maintenance of quality of life (QOL) of the elderly.
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Polyamines regulate gene expression by stimulating translation of histone acetyltransferase mRNAs. 査読あり
Sakamoto Akihiko, Terui Yusuke, Uemura Takeshi, Igarashi Kazuei, Kashiwagi Keiko
J Biol Chem 295 ( 26 ) 8736 - 8745 2020年06月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Polyamines regulate gene expression in Escherichia coli by translationally stimulating mRNAs encoding global transcription factors. In this study, we focused on histone acetylation, one of the mechanisms of epigenetic regulation of gene expression, to attempt to clarify the role of polyamines in the regulation of gene expression in eukaryotes. We found that activities of histone acetyltransferases in both the nucleus and cytoplasm decreased significantly in polyamine-reduced mouse mammary carcinoma FM3A cells. Although protein levels of histones H3 and H4 did not change in control and polyamine-reduced cells, acetylation of histones H3 and H4 was greatly decreased in the polyamine-reduced cells. Next, we used control and polyamine-reduced cells to identify histone acetyltransferases whose synthesis is stimulated by polyamines. We found that polyamines stimulate the translation of histone acetyltransferases GCN5 and HAT1. Accordingly, GCN5- and HAT1-catalyzed acetylation of specific lysine residues on histones H3 and H4 was stimulated by polyamines. Consistent with these findings, transcription of genes required for cell proliferation was enhanced by polyamines. These results indicate that polyamines regulate gene expression by enhancing the expression of the histone acetyltransferases GCN5 and HAT1 at the level of translation. Mechanistically, polyamines enhanced the interaction of microRNA-7648-5p (miR-7648-5p) with the 5'-UTR of GCN5 mRNA, resulting in stimulation of translation due to the destabilization of the double-stranded RNA (dsRNA) between the 5'-UTR and the ORF of GCN5 mRNA. Because HAT1 mRNA has a short 5'-UTR, polyamines may enhance initiation complex formation directly on this mRNA.
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Cytotoxic Mechanism of Excess Polyamines Functions through Translational Repression of Specific Proteins Encoded by Polyamine Modulon. 査読あり
Sakamoto Akihiko, Sahara Junpei, Kawai Gota, Yamamoto Kaneyoshi, Ishihama Akira, Uemura Takeshi, Igarashi Kazuei, Kashiwagi Keiko, Terui Yusuke
Int J Mol Sci 21 ( 7 ) 2020年03月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Excessive accumulation of polyamines causes cytotoxicity, including inhibition of cell growth and a decrease in viability. We investigated the mechanism of cytotoxicity caused by spermidine accumulation under various conditions using an Escherichia coli strain deficient in spermidine acetyltransferase (SAT), a key catabolic enzyme in controlling polyamine levels. Due to the excessive accumulation of polyamines by the addition of exogenous spermidine to the growth medium, cell growth and viability were markedly decreased through translational repression of specific proteins [RMF (ribosome modulation factor) and Fis (rRNA transcription factor) etc.] encoded by members of polyamine modulon, which are essential for cell growth and viability. In particular, synthesis of proteins that have unusual locations of the Shine-Dalgarno (SD) sequence in their mRNAs was inhibited. In order to elucidate the molecular mechanism of cytotoxicity by the excessive accumulation of spermidine, the spermidine-dependent structural change of the bulged-out region in the mRNA at the initiation site of the rmf mRNA was examined using NMR analysis. It was suggested that the structure of the mRNA bulged-out region is affected by excess spermidine, so the SD sequence of the rmf mRNA cannot approach initiation codon AUG.
DOI： 10.3390/ijms21072406
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Assessing acrolein for determination of the severity of brain stroke, dementia, renal failure, and Sjögren's syndrome. 査読あり
Igarashi Kazuei, Uemura Takeshi, Kashiwagi Keiko
Amino Acids 52 ( 2 ) 119 - 127 2020年02月
記述言語：英語 掲載種別：研究論文（学術雑誌）
It was found recently that acrolein (CH(2)=CH-CHO), mainly produced from spermine, is more toxic than ROS (reactive oxygen species, O(2)(-·), H(2)O(2), and ·OH). In this review, we describe how the seriousness of brain infarction, dementia, renal failure, and Sjӧgren's syndrome is correlated with acrolein. In brain infarction and dementia, it was possible to identify incipient patients with high sensitivity and specificity by measuring protein-conjugated acrolein (PC-Acro) in plasma together with IL-6 and CRP in brain infarction and Aβ(40/42) in dementia. The level of PC-Acro in plasma and saliva correlated with the seriousness of renal failure and Sjӧgren's syndrome, respectively. Thus, development of acrolein scavenger medicines containing SH-group such as N-acetylcysteine derivatives is important to maintain QOL (quality of life) of the elderly.
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蛋白質抱合アクロレイン、IL-6並びにCRP測定に基づく脳梗塞リスク評価による脳梗塞発症者数の減少 査読あり
五十嵐一衛、植村武史、柏木敬子
未病と抗老化 29 30 - 34 2020年
担当区分：第二著者 記述言語：日本語 掲載種別：研究論文（学術雑誌）
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GSTΠ stimulates caveolin-1-regulated polyamine uptake via actin remodeling. 査読あり
Uemura Takeshi, Tsaprailis George, Gerner Eugene W
Oncotarget 10 ( 55 ) 5713 - 5723 2019年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Polyamines spermidine and spermine, and their diamine precursor putrescine, are essential for normal cellular functions in both pro- and eukaryotes. Cellular polyamine levels are regulated by biosynthesis, degradation and transport. Transport of dietary and luminal bacterial polyamines in gastrointestinal (GI) tissues plays a significant role in tissue polyamine homeostasis. We have reported that caveolin-1 play an inhibitory role in polyamine uptake in GI tissues. We investigated the mechanism of caveolin-1-regulated polyamine transport. We found that glutathione S-transferase Π(GSTΠ) was secreted from caveolin-1 knockdown cells and stimulated spermidine transport in human colon-derived HCT116 cells. GSTΠ secreted in the medium increased S-glutathionylated protein level in the plasma membrane fraction. Proteomic analysis revealed that actin was S-glutathionylated by GSTΠ. Immunofluorescence microscopy demonstrated that actin filaments around plasma membrane were S-glutathionylated in caveolin-1 knockdown cells. Inhibition of actin remodeling by jasplakinolide caused a decrease in polyamine uptake activity. These data support a model in which caveolin-1 negatively regulates polyamine uptake by inhibiting GSTΠ secretion, which stimulates actin remodeling and endocytosis.
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Inhibition of dendritic spine extension through acrolein conjugation with α-, β-tubulin proteins. 査読あり
Uemura Takeshi, Suzuki Takehiro, Ko Kenta, Watanabe Kenta, Dohmae Naoshi, Sakamoto Akihiko, Terui Yusuke, Toida Toshihiko, Kashiwagi Keiko, Igarashi Kazuei
Int J Biochem Cell Biol 113 58 - 66 2019年08月
記述言語：英語 掲載種別：研究論文（学術雑誌）
We have recently found that conjugation of acrolein with a 50 kDa protein(s) is strongly associated with tissue damage during brain infarction. In the current study, the identity and function of the 50 kDa protein(s) conjugated with acrolein during brain infarction were investigated. The 50 kDa protein(s) conjugated with acrolein were identified as α- and β-tubulins. Ten cysteine residues in α- and β-tubulins (Cys25, 295, 347 and 376 in α-tubulin and Cys12, 129, 211, 239, 303 and 354 in β-tubulin) were mainly conjugated with acrolein. Since two cysteine residues of α-tubulin (Cys347 and 376) and four cysteine residues of β-tubulin (Cys12, 129, 239 and 354) were located at the interaction site of α- and β-tubulins, association between α- and β-tubulins to form microtubules was strongly inhibited by conjugation with acrolein. Accordingly, dendritic spine extension consisting of microtubules was greatly inhibited in acrolein-treated Neuro2a cells. The results strongly suggest that acrolein contributes to the functional losses in brain signaling through its conjugation with α- and β-tubulins.
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Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing. 査読あり
Lim Hui Kheng, Rahim Anisa B, Leo Vonny Ivon, Das Shatarupa, Lim Thiam Chye, Uemura Takeshi, Igarashi Kazuei, Common John, Vardy Leah A
J Invest Dermatol 138 ( 12 ) 2653 - 2665 2018年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Wound healing is a dynamic process involving gene-expression changes that drive re-epithelialization. Here, we describe an essential role for polyamine regulator AMD1 in driving cell migration at the wound edge. The polyamines, putrescine, spermidine, and spermine are small cationic molecules that play essential roles in many cellular processes. We demonstrate that AMD1 is rapidly upregulated following wounding in human skin biopsies. Knockdown of AMD1 with small hairpin RNAs causes a delay in cell migration that is rescued by the addition of spermine. We further show that spermine can promote cell migration in keratinocytes and in human ex vivo wounds, where it significantly increases epithelial tongue migration. Knockdown of AMD1 prevents the upregulation of urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor on wounding and results in a failure in actin cytoskeletal reorganization at the wound edge. We demonstrate that keratinocytes respond to wounding by modulating polyamine regulator AMD1 in order to regulate downstream gene expression and promote cell migration. This article highlights a previously unreported role for the regulation of polyamine levels and ratios in cellular behavior and fate.