دورية أكاديمية
Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis.
العنوان: | Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis. |
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المؤلفون: | Jeung D; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Lee GE; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Chen W; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Byun J; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Nam SB; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea.; Biopharmaceutical research center, Ochang Institute of Biological and Environmental Science, Korea Basic Science Institute, 162, Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, 28119, Republic of Korea., Park YM; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Lee HS; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Kang HC; College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Lee JY; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea., Kim KD; Division of Life Sciences, Gyeongsang National University, 501, Jinju-daero, Jinju-si, Gyeongsangnam-do, 52828, South Korea., Hong YS; Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, 30, Yeongudanji-ro, Ochang-eup, Cheongju-si, Chongbuk, 28116, South Korea., Lee CJ; Biopharmaceutical research center, Ochang Institute of Biological and Environmental Science, Korea Basic Science Institute, 162, Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, 28119, Republic of Korea., Kim DJ; Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, MBMRF, 1.410, 5300, North L St., McAllen, TX, 78504, USA., Cho YY; BK21-4Th Team, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, South Korea. yongyeon@catholic.ac.kr. |
المصدر: | Scientific reports [Sci Rep] 2024 Apr 24; Vol. 14 (1), pp. 9440. Date of Electronic Publication: 2024 Apr 24. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Ribosomal Protein S6 Kinases, 90-kDa*/metabolism , Ribosomal Protein S6 Kinases, 90-kDa*/genetics , Melanins*/biosynthesis , Melanins*/metabolism , alpha-MSH*/metabolism , alpha-MSH*/pharmacology , Signal Transduction* , Pteridines*, Animals ; Mice ; Cell Line, Tumor ; Forkhead Transcription Factors/metabolism ; Forkhead Transcription Factors/genetics ; Ultraviolet Rays ; Morpholines/pharmacology ; Chromones/pharmacology ; Nitriles/pharmacology ; Butadienes/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Melanoma, Experimental/metabolism ; Melanogenesis |
مستخلص: | Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4's transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis. (© 2024. The Author(s).) |
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معلومات مُعتمدة: | 2023R1A2C2003059 Ministry of Science, ICT and Future Planning |
فهرسة مساهمة: | Keywords: FOXO4; FOXO4 activity; Melanogenesis; RSK2; Signaling pathway |
المشرفين على المادة: | EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa) 0 (Melanins) 581-05-5 (alpha-MSH) 0 (Forkhead Transcription Factors) 0 (Morpholines) 0 (BI D1870) 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) 0 (Chromones) 0 (Nitriles) 0 (Butadienes) 0 (U 0126) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 2.7.11.1 (ribosomal protein S6 kinase, 90kDa, polypeptide 3) 0 (Pteridines) |
تواريخ الأحداث: | Date Created: 20240424 Date Completed: 20240424 Latest Revision: 20240530 |
رمز التحديث: | 20240531 |
مُعرف محوري في PubMed: | PMC11043394 |
DOI: | 10.1038/s41598-024-60165-9 |
PMID: | 38658799 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-024-60165-9 |