{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:32:01Z","timestamp":1791289921059,"version":"4.3.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100018749","name":"Korea Brain Research Institute","doi-asserted-by":"publisher","award":["22-BR-01-02"],"award-info":[{"award-number":["22-BR-01-02"]}],"id":[{"id":"10.13039\/100018749","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003627","name":"Rural Development Administration","doi-asserted-by":"publisher","award":["PJ014868042022"],"award-info":[{"award-number":["PJ014868042022"]}],"id":[{"id":"10.13039\/501100003627","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gyeonggido Business & Science Accelerator"},{"name":"Korea Initiative for fostering University of Research and Innovation Program of the National Research Foundation","award":["NRF2021M3H1A104892211"],"award-info":[{"award-number":["NRF2021M3H1A104892211"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019005607"],"award-info":[{"award-number":["2019005607"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ajou University Research Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spermidine (SPD), a polyamine naturally present in living organisms, is known to prolong the\u00a0lifespan of animals. In this study, the role of SPD in melanogenesis was investigated, showing potential\u00a0as a pigmenting agent. SPD treatment increased melanin production in melanocytes in a dose dependent manner. Computational analysis with RNA-sequencing data revealed the alteration of protein degradation by SPD treatment without changes\u00a0in the expressions of melanogenesis-related genes. Indeed, SPD treatment significantly increased the stabilities of tyrosinase-related protein (TRP)-1 and -2 while inhibiting ubiquitination, which was confirmed by treatment of proteasome inhibitor MG132. Inhibition of protein synthesis by cycloheximide (CHX) showed that SPD treatment increased the resistance of TRP-1 and TRP-2 to protein degradation. To identify the proteins involved in SPD transportation in melanocytes, the expression of several solute carrier (SLC) membrane transporters was assessed and, among 27 transporter genes, SLC3A2, SLC7A1, SLC18B1, and SLC22A18 were highly expressed, implying they are putative SPD transporters in melanocytes. Furthermore, SLC7A1 and SLC22A18 were downregulated by SPD treatment, indicating their active involvement in polyamine homeostasis. Finally, we applied SPD to a human skin equivalent and observed elevated melanin production. Our results identify SPD as a potential natural product to alleviate hypopigmentation.<\/jats:p>","DOI":"10.1038\/s41598-022-18629-3","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T10:04:48Z","timestamp":1661421888000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A systematic exploration reveals the potential of spermidine for hypopigmentation treatment through the stabilization of melanogenesis-associated proteins"],"prefix":"10.1038","volume":"12","author":[{"given":"Sofia","family":"Brito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyojin","family":"Heo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byungsun","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sehyun","family":"Chae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Gi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong-Mun","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bum-Ho","family":"Bin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"18629_CR1","first-page":"109","volume":"79","author":"S Plensdorf","year":"2009","unstructured":"Plensdorf, S. & Martinez, J. Common pigmentation disorders. Am. Fam. Phys. 79, 109\u2013116 (2009).","journal-title":"Am. Fam. Phys."},{"key":"18629_CR2","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1610-0387.2009.07137.x","volume":"8","author":"SK Fistarol","year":"2010","unstructured":"Fistarol, S. K. & Itin, P. H. Disorders of pigmentation. J. German Soc. Dermatol. 8, 187\u2013201. https:\/\/doi.org\/10.1111\/j.1610-0387.2009.07137.x (2010) (quiz 201\u2013182).","journal-title":"J. German Soc. Dermatol."},{"key":"18629_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0531-5565(00)00210-2","volume":"36","author":"DJ Tobin","year":"2001","unstructured":"Tobin, D. J. & Paus, R. Graying: Gerontobiology of the hair follicle pigmentary unit. Exp. Gerontol. 36, 29\u201354 (2001).","journal-title":"Exp. Gerontol."},{"key":"18629_CR4","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/s0738-081x(03)00045-2","volume":"21","author":"JV Schaffer","year":"2003","unstructured":"Schaffer, J. V. & Bolognia, J. L. The treatment of hypopigmentation in children. Clin. Dermatol. 21, 296\u2013310. https:\/\/doi.org\/10.1016\/s0738-081x(03)00045-2 (2003).","journal-title":"Clin. Dermatol."},{"key":"18629_CR5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1365-2133.1976.tb02268.x","volume":"94","author":"SS Bleehen","year":"1976","unstructured":"Bleehen, S. S. The treatment of vitiligo with topical corticosteroids. Light and electronmicroscopic studies. Br. J. Dermatol. 94, 43\u201350 (1976).","journal-title":"Br. J. Dermatol."},{"key":"18629_CR6","doi-asserted-by":"publisher","first-page":"416","DOI":"10.4103\/2229-5178.142483","volume":"5","author":"A Coondoo","year":"2014","unstructured":"Coondoo, A., Phiske, M., Verma, S. & Lahiri, K. Side-effects of topical steroids: A long overdue revisit. Indian Dermatol. Online J. 5, 416 (2014).","journal-title":"Indian Dermatol. Online J."},{"key":"18629_CR7","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S0190-9622(84)70155-1","volume":"11","author":"JL S\u00e1nchez","year":"1984","unstructured":"S\u00e1nchez, J. L. & Torres, V. M. Double-blind efficacy study of selenium sulfide in tinea versicolor. J. Am. Acad. Dermatol. 11, 235\u2013238 (1984).","journal-title":"J. Am. Acad. Dermatol."},{"key":"18629_CR8","first-page":"425","volume":"73","author":"CA Hull","year":"2004","unstructured":"Hull, C. A. & Johnson, S. M. A double-blind comparative study of sodium sulfacetamide lotion 10% versus selenium sulfide lotion 2.5% in the treatment of pityriasis (tinea) versicolor. Cutis 73, 425\u2013429 (2004).","journal-title":"Cutis"},{"key":"18629_CR9","doi-asserted-by":"publisher","first-page":"h1394","DOI":"10.1136\/bmj.h1394","volume":"350","author":"S Renati","year":"2015","unstructured":"Renati, S., Cukras, A. & Bigby, M. Pityriasis versicolor. BMJ 350, h1394. https:\/\/doi.org\/10.1136\/bmj.h1394 (2015).","journal-title":"BMJ"},{"key":"18629_CR10","first-page":"44","volume":"35","author":"JA Kyle","year":"2010","unstructured":"Kyle, J. A. The fungus among us: An antifungal review. US Pharm. 35, 44\u201356 (2010).","journal-title":"US Pharm."},{"key":"18629_CR11","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1016\/j.bbagen.2018.06.004","volume":"1862","author":"D-H Bae","year":"2018","unstructured":"Bae, D.-H., Lane, D. J., Jansson, P. J. & Richardson, D. R. The old and new biochemistry of polyamines. Biochim. Biophys. Acta Gen. Subjects 1862, 2053\u20132068 (2018).","journal-title":"Biochim. Biophys. Acta Gen. Subjects"},{"key":"18629_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-020-01545-9","volume":"20","author":"J Li","year":"2020","unstructured":"Li, J., Meng, Y., Wu, X. & Sun, Y. Polyamines and related signaling pathways in cancer. Cancer Cell Int. 20, 1\u201316 (2020).","journal-title":"Cancer Cell Int."},{"key":"18629_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4062\/biomolther.2012.097","volume":"21","author":"MH Park","year":"2013","unstructured":"Park, M. H. & Igarashi, K. Polyamines and their metabolites as diagnostic markers of human diseases. Biomol. Ther. 21, 1 (2013).","journal-title":"Biomol. Ther."},{"key":"18629_CR14","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan2788","author":"F Madeo","year":"2018","unstructured":"Madeo, F., Eisenberg, T., Pietrocola, F. & Kroemer, G. Spermidine in health and disease. Science https:\/\/doi.org\/10.1126\/science.aan2788 (2018).","journal-title":"Science"},{"key":"18629_CR15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.biocel.2009.07.009","volume":"42","author":"K Igarashi","year":"2010","unstructured":"Igarashi, K. & Kashiwagi, K. Modulation of cellular function by polyamines. Int. J. Biochem. Cell Biol. 42, 39\u201351 (2010).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"18629_CR16","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1079\/BJN19950087","volume":"73","author":"S Bard\u00f3cz","year":"1995","unstructured":"Bard\u00f3cz, S. et al. The importance of dietary polyamines in cell regeneration and growth. Br. J. Nutr. 73, 819\u2013828 (1995).","journal-title":"Br. J. Nutr."},{"key":"18629_CR17","doi-asserted-by":"publisher","DOI":"10.3402\/fnr.v55i0.5572","author":"M Atiya Ali","year":"2011","unstructured":"Atiya Ali, M., Poortvliet, E., Stromberg, R. & Yngve, A. Polyamines in foods: Development of a food database. Food Nutr. Res. https:\/\/doi.org\/10.3402\/fnr.v55i0.5572 (2011).","journal-title":"Food Nutr. Res."},{"key":"18629_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2019.00108","author":"NC Mu\u00f1oz-Esparza","year":"2019","unstructured":"Mu\u00f1oz-Esparza, N. C. et al. Polyamines in food. Front. Nutr. https:\/\/doi.org\/10.3389\/fnut.2019.00108 (2019).","journal-title":"Front. Nutr."},{"key":"18629_CR19","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1146\/annurev-nutr-120419-015419","volume":"40","author":"F Madeo","year":"2020","unstructured":"Madeo, F. et al. Nutritional aspects of spermidine. Annu. Rev. Nutr. 40, 135\u2013159 (2020).","journal-title":"Annu. Rev. Nutr."},{"key":"18629_CR20","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1080\/15548627.2018.1530929","volume":"15","author":"F Madeo","year":"2019","unstructured":"Madeo, F., Bauer, M. A., Carmona-Gutierrez, D. & Kroemer, G. Spermidine: A physiological autophagy inducer acting as an anti-aging vitamin in humans?. Autophagy 15, 165\u2013168 (2019).","journal-title":"Autophagy"},{"key":"18629_CR21","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.18632\/aging.101517","volume":"10","author":"F Madeo","year":"2018","unstructured":"Madeo, F., Carmona-Gutierrez, D., Kepp, O. & Kroemer, G. Spermidine delays aging in humans. Aging 10, 2209 (2018).","journal-title":"Aging"},{"key":"18629_CR22","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.3390\/ma5091661","volume":"5","author":"T-S Chang","year":"2012","unstructured":"Chang, T.-S. Natural melanogenesis inhibitors acting through the down-regulation of tyrosinase activity. Materials 5, 1661\u20131685 (2012).","journal-title":"Materials"},{"key":"18629_CR23","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/S0022-2275(20)33493-3","volume":"40","author":"H Ando","year":"1999","unstructured":"Ando, H. et al. Possible involvement of proteolytic degradation of tyrosinase in the regulatory effect of fatty acids on melanogenesis. J. Lipid Res. 40, 1312\u20131316 (1999).","journal-title":"J. Lipid Res."},{"key":"18629_CR24","doi-asserted-by":"publisher","first-page":"5818","DOI":"10.1002\/j.1460-2075.1994.tb06925.x","volume":"13","author":"T Kobayashi","year":"1994","unstructured":"Kobayashi, T. et al. Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J. 13, 5818\u20135825 (1994).","journal-title":"EMBO J."},{"key":"18629_CR25","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1002\/j.1460-2075.1992.tb05082.x","volume":"11","author":"K Tsukamoto","year":"1992","unstructured":"Tsukamoto, K., Jackson, I. J., Urabe, K., Montague, P. M. & Hearing, V. A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase. EMBO J. 11, 519\u2013526 (1992).","journal-title":"EMBO J."},{"key":"18629_CR26","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/sj.jid.5700683","volume":"127","author":"H Ando","year":"2007","unstructured":"Ando, H., Kondoh, H., Ichihashi, M. & Hearing, V. J. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J. Investig. Dermatol. 127, 751\u2013761 (2007).","journal-title":"J. Investig. Dermatol."},{"key":"18629_CR27","doi-asserted-by":"publisher","first-page":"4428","DOI":"10.3390\/ijms10104428","volume":"10","author":"H Ando","year":"2009","unstructured":"Ando, H., Ichihashi, M. & Hearing, V. J. Role of the ubiquitin proteasome system in regulating skin pigmentation. Int. J. Mol. Sci. 10, 4428\u20134434 (2009).","journal-title":"Int. J. Mol. Sci."},{"key":"18629_CR28","doi-asserted-by":"publisher","first-page":"9632","DOI":"10.1021\/acs.jpcb.6b06648","volume":"120","author":"L Momeni","year":"2016","unstructured":"Momeni, L., Shareghi, B., Saboury, A. A. & Farhadian, S. Comparative studies on the interaction of spermidine with bovine trypsin by multispectroscopic and docking methods. J. Phys. Chem. B 120, 9632\u20139641 (2016).","journal-title":"J. Phys. Chem. B"},{"key":"18629_CR29","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.ijbiomac.2019.03.084","volume":"131","author":"S Sadeghi-Kaji","year":"2019","unstructured":"Sadeghi-Kaji, S., Shareghi, B., Saboury, A. A. & Farhadian, S. Spectroscopic and molecular docking studies on the interaction between spermidine and pancreatic elastase. Int. J. Biol. Macromol. 131, 473\u2013483 (2019).","journal-title":"Int. J. Biol. Macromol."},{"key":"18629_CR30","doi-asserted-by":"publisher","first-page":"105476","DOI":"10.1039\/C6RA20975K","volume":"6","author":"M Hosseini-Koupaei","year":"2016","unstructured":"Hosseini-Koupaei, M., Shareghi, B., Saboury, A. A., Davar, F. & Raisi, F. The effect of spermidine on the structure, kinetics and stability of proteinase K: Spectroscopic and computational approaches. RSC Adv. 6, 105476\u2013105486 (2016).","journal-title":"RSC Adv."},{"key":"18629_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0149-3","volume":"50","author":"PK Sacitharan","year":"2018","unstructured":"Sacitharan, P. K., Lwin, S., Gharios, G. B. & Edwards, J. R. Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300. Exp. Mol. Med. 50, 1\u201310 (2018).","journal-title":"Exp. Mol. Med."},{"key":"18629_CR32","doi-asserted-by":"publisher","first-page":"6210","DOI":"10.1073\/pnas.94.12.6210","volume":"94","author":"R Halaban","year":"1997","unstructured":"Halaban, R. et al. Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proc. Natl. Acad. Sci. 94, 6210\u20136215 (1997).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"18629_CR33","doi-asserted-by":"publisher","first-page":"716","DOI":"10.18632\/aging.100361","volume":"3","author":"N Minois","year":"2011","unstructured":"Minois, N., Carmona-Gutierrez, D. & Madeo, F. Polyamines in aging and disease. Aging 3, 716 (2011).","journal-title":"Aging"},{"key":"18629_CR34","doi-asserted-by":"publisher","first-page":"G517","DOI":"10.1152\/ajpgi.00169.2010","volume":"299","author":"T Uemura","year":"2010","unstructured":"Uemura, T., Stringer, D. E., Blohm-Mangone, K. A. & Gerner, E. W. Polyamine transport is mediated by both endocytic and solute carrier transport mechanisms in the gastrointestinal tract. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G517\u2013G522 (2010).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"18629_CR35","doi-asserted-by":"publisher","first-page":"49355","DOI":"10.1074\/jbc.M401287200","volume":"279","author":"D Soulet","year":"2004","unstructured":"Soulet, D., Gagnon, B., Rivest, S., Audette, M. & Poulin, R. A fluorescent probe of polyamine transport accumulates into intracellular acidic vesicles via a two-step mechanism. J. Biol. Chem. 279, 49355\u201349366. https:\/\/doi.org\/10.1074\/jbc.M401287200 (2004).","journal-title":"J. Biol. Chem."},{"key":"18629_CR36","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s00726-013-1553-6","volume":"46","author":"AA Abdulhussein","year":"2014","unstructured":"Abdulhussein, A. A. & Wallace, H. M. Polyamines and membrane transporters. Amino Acids 46, 655\u2013660. https:\/\/doi.org\/10.1007\/s00726-013-1553-6 (2014).","journal-title":"Amino Acids"},{"key":"18629_CR37","doi-asserted-by":"publisher","first-page":"3909","DOI":"10.1074\/jbc.M116.756197","volume":"292","author":"T Takeuchi","year":"2017","unstructured":"Takeuchi, T. et al. Vesicular polyamine transporter mediates vesicular storage and release of polyamine from mast cells. J. Biol. Chem. 292, 3909\u20133918. https:\/\/doi.org\/10.1074\/jbc.M116.756197 (2017).","journal-title":"J. Biol. Chem."},{"key":"18629_CR38","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s00726-011-0987-y","volume":"42","author":"R Poulin","year":"2012","unstructured":"Poulin, R., Casero, R. A. & Soulet, D. Recent advances in the molecular biology of metazoan polyamine transport. Amino Acids 42, 711\u2013723. https:\/\/doi.org\/10.1007\/s00726-011-0987-y (2012).","journal-title":"Amino Acids"},{"key":"18629_CR39","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1097\/00029330-200710010-00013","volume":"120","author":"W-K Hou","year":"2007","unstructured":"Hou, W.-K. et al. Influence of blood glucose on the expression of glucose transporter proteins 1 and 3 in the brain of diabetic rats. Chin. Med. J. 120, 1704\u20131709 (2007).","journal-title":"Chin. Med. J."},{"key":"18629_CR40","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1093\/jb\/mvj003","volume":"139","author":"K Nishimura","year":"2006","unstructured":"Nishimura, K., Shiina, R., Kashiwagi, K. & Igarashi, K. Decrease in polyamines with aging and their ingestion from food and drink. J. Biochem. 139, 81\u201390. https:\/\/doi.org\/10.1093\/jb\/mvj003 (2006).","journal-title":"J. Biochem."},{"key":"18629_CR41","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/j.1365-2133.1990.tb16121.x","volume":"122","author":"JP Ortonne","year":"1990","unstructured":"Ortonne, J. P. Pigmentary changes of the ageing skin. Br. J. Dermatol. 122, 21\u201328 (1990).","journal-title":"Br. J. Dermatol."},{"key":"18629_CR42","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/S0899-9007(97)00190-1","volume":"13","author":"M Jeevanandam","year":"1997","unstructured":"Jeevanandam, M., Holaday, N. J., Begay, C. K. & Petersen, S. R. Nutritional efficacy of a spermidine supplemented diet. Nutrition 13, 788\u2013794 (1997).","journal-title":"Nutrition"},{"key":"18629_CR43","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1016\/j.jid.2017.03.024","volume":"137","author":"EY Seo","year":"2017","unstructured":"Seo, E. Y. et al. UCHL1 regulates melanogenesis through controlling MITF stability in human melanocytes. J. Investig. Dermatol. 137, 1757\u20131765 (2017).","journal-title":"J. Investig. Dermatol."},{"key":"18629_CR44","doi-asserted-by":"publisher","first-page":"27774","DOI":"10.1074\/jbc.M401786200","volume":"279","author":"A Kageyama","year":"2004","unstructured":"Kageyama, A. et al. Down-regulation of melanogenesis by phospholipase D2 through ubiquitin proteasome-mediated degradation of tyrosinase. J. Biol. Chem. 279, 27774\u201327780 (2004).","journal-title":"J. Biol. Chem."},{"key":"18629_CR45","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/1873-3468.13299","volume":"593","author":"E Sayas","year":"2019","unstructured":"Sayas, E. et al. Polyamines interfere with protein ubiquitylation and cause depletion of intracellular amino acids: A possible mechanism for cell growth inhibition. FEBS Lett. 593, 209\u2013218 (2019).","journal-title":"FEBS Lett."},{"key":"18629_CR46","doi-asserted-by":"publisher","first-page":"31801","DOI":"10.1074\/jbc.273.48.31801","volume":"273","author":"T Kobayashi","year":"1998","unstructured":"Kobayashi, T., Imokawa, G., Bennett, D. C. & Hearing, V. J. Tyrosinase stabilization by Tyrp1 (the brown locus protein). J. Biol. Chem. 273, 31801\u201331805 (1998).","journal-title":"J. Biol. Chem."},{"key":"18629_CR47","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/nrc1881","volume":"6","author":"KI Nakayama","year":"2006","unstructured":"Nakayama, K. I. & Nakayama, K. Ubiquitin ligases: Cell-cycle control and cancer. Nat. Rev. Cancer 6, 369\u2013381 (2006).","journal-title":"Nat. Rev. Cancer"},{"key":"18629_CR48","doi-asserted-by":"publisher","first-page":"15427","DOI":"10.1074\/jbc.M313701200","volume":"279","author":"H Ando","year":"2004","unstructured":"Ando, H. et al. Fatty acids regulate pigmentation via proteasomal degradation of tyrosinase: A new aspect of ubiquitin-proteasome function. J. Biol. Chem. 279, 15427\u201315433 (2004).","journal-title":"J. Biol. Chem."},{"key":"18629_CR49","doi-asserted-by":"publisher","first-page":"e102435","DOI":"10.1371\/journal.pone.0102435","volume":"9","author":"N Minois","year":"2014","unstructured":"Minois, N., Rockenfeller, P., Smith, T. K. & Carmona-Gutierrez, D. Spermidine feeding decreases age-related locomotor activity loss and induces changes in lipid composition. PLoS ONE 9, e102435 (2014).","journal-title":"PLoS ONE"},{"key":"18629_CR50","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/pcmr.12838","volume":"33","author":"JY Kim","year":"2020","unstructured":"Kim, J. Y. et al. Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes. Pigment Cell Melanoma Res. 33, 403\u2013415 (2020).","journal-title":"Pigment Cell Melanoma Res."},{"key":"18629_CR51","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00726-009-0400-2","volume":"38","author":"AJ Palmer","year":"2010","unstructured":"Palmer, A. J. & Wallace, H. M. The polyamine transport system as a target for anticancer drug development. Amino Acids 38, 415\u2013422 (2010).","journal-title":"Amino Acids"},{"key":"18629_CR52","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3390\/biom10040499","volume":"10","author":"M Corral","year":"2020","unstructured":"Corral, M. & Wallace, H. M. Upregulation of polyamine transport in human colorectal cancer cells. Biomolecules 10, 499 (2020).","journal-title":"Biomolecules"},{"key":"18629_CR53","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1093\/molbev\/msq350","volume":"28","author":"PJ H\u00f6glund","year":"2011","unstructured":"H\u00f6glund, P. J., Nordstr\u00f6m, K. J., Schi\u00f6th, H. B. & Fredriksson, R. The solute carrier families have a remarkably long evolutionary history with the majority of the human families present before divergence of Bilaterian species. Mol. Biol. Evol. 28, 1531\u20131541 (2011).","journal-title":"Mol. Biol. Evol."},{"key":"18629_CR54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep05251","volume":"4","author":"R Fujiwara","year":"2014","unstructured":"Fujiwara, R., Takenaka, S., Hashimoto, M., Narawa, T. & Itoh, T. Expression of human solute carrier family transporters in skin: Possible contributor to drug-induced skin disorders. Sci. Rep. 4, 1\u20138 (2014).","journal-title":"Sci. Rep."},{"key":"18629_CR55","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1515\/ntrev-2016-0081","volume":"6","author":"K Sejwal","year":"2017","unstructured":"Sejwal, K. et al. Proteoliposomes\u2014A system to study membrane proteins under buffer gradients by cryo-EM. Nanotechnol. Rev. 6, 57\u201374 (2017).","journal-title":"Nanotechnol. Rev."},{"key":"18629_CR56","doi-asserted-by":"publisher","first-page":"e105965","DOI":"10.1371\/journal.pone.0105965","volume":"9","author":"BH Bin","year":"2014","unstructured":"Bin, B. H. et al. Hyperosmotic stress reduces melanin production by altering melanosome formation. PLoS ONE 9, e105965. https:\/\/doi.org\/10.1371\/journal.pone.0105965 (2014).","journal-title":"PLoS ONE"},{"key":"18629_CR57","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14806\/ej.17.1.200","volume":"17","author":"M Martin","year":"2011","unstructured":"Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10\u201312 (2011).","journal-title":"EMBnet J."},{"key":"18629_CR58","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","volume":"25","author":"C Trapnell","year":"2009","unstructured":"Trapnell, C., Pachter, L. & Salzberg, S. L. TopHat: Discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105\u20131111 (2009).","journal-title":"Bioinformatics"},{"key":"18629_CR59","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders, S., Pyl, P. T. & Huber, W. HTSeq\u2014A Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166\u2013169 (2015).","journal-title":"Bioinformatics"},{"key":"18629_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gb-2010-11-3-r25","volume":"11","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, 1\u20139 (2010).","journal-title":"Genome Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-18629-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-18629-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-18629-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,26]],"date-time":"2023-11-26T05:10:52Z","timestamp":1700975452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-18629-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,25]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["18629"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-18629-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,25]]},"assertion":[{"value":"4 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14478"}}