Syndecan-2 regulates melanin synthesis via protein kinase C βII-mediated tyrosinase activation.
Syndecan-2, a transmembrane heparan sulfate proteoglycan that is highly expressed in melanoma cells, regulates melanoma cell functions (e.g. migration). Since melanoma is a malignant tumor of melanocytes, which largely function to synthesize melanin, we investigated the possible involvement of syndecan-2 in melanogenesis. Syndecan-2 expression was increased in human skin melanoma tissues compared with normal skin. In both mouse and human melanoma cells, siRNA-mediated knockdown of syndecan-2 was associated with reduced melanin synthesis, whereas overexpression of syndecan-2 increased melanin synthesis. Similar effects were also detected in human primary epidermal melanocytes. Syndecan-2 expression did not affect the expression of tyrosinase, a key enzyme in melanin synthesis, but instead enhanced the enzymatic activity of tyrosinase by increasing the membrane and melanosome localization of its regulator, protein kinase CβII. Furthermore, UVB caused increased syndecan-2 expression, and this up-regulation of syndecan-2 was required for UVB-induced melanin synthesis. Taken together, these data suggest that syndecan-2 regulates melanin synthesis and could be a potential therapeutic target for treating melanin-associated diseases.
Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Center for Cellular Homeostasis, Ewha Womans University, Seoul, Korea.
Hyejung
H
Jung
Heesung
H
Chung
Sung Eun
SE
Chang
Sora
S
Choi
Inn-Oc
IO
Han
Duk-Hee
DH
Kang
Eok-Soo
ES
Oh
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism* / Q000528:radiation effects; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D020460:Melanosomes / Q000201:enzymology; D051379:Mice; D058990:Molecular Targeted Therapy; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D064546:Protein Kinase C beta / Q000502:physiology*; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D053669:Syndecan-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects
D008543:Melanins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C508246:Sdc2 protein, mouse; D053669:Syndecan-2; D014442:Monophenol Monooxygenase; D064546:Protein Kinase C beta
melanogenesis; melanosome; protein kinase C β; syndecan-2; tyrosinase