2010年12月
Downregulation of SIK2 expression promotes the melanogenic program in mice
PIGMENT CELL & MELANOMA RESEARCH
- 巻
- 23
- 号
- 6
- 開始ページ
- 809
- 終了ページ
- 819
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1755-148X.2010.00760.x
- 出版者・発行元
- WILEY-BLACKWELL
P>cAMP response element-binding protein (CREB) promotes melanogenesis by inducing microphthalmia-associated transcription factor (Mitf ) gene expression. We report here that the CREB-specific coactivator TORC and its repressor, salt-inducible kinase 2 (SIK2), are fundamental determinants of the melanogenic program in mice. Exposure of B16 melanoma cells to ultraviolet (UV) light results in the immediate nuclear translocation of TORC1, which is inhibited by SIK2. Overexpression of dominant-negative TORC1 also inhibits UV-induced Mitf gene expression and melanogenesis. alpha-MSH signaling regulates hair pigmentation, and the decrease in alpha-MSH activity in hair follicle melanocytes switches the melanin synthesis from eumelanin (black) to pheomelanin (yellow). Mice with the lethal yellow allele of agouti (Ay) have yellow hair because of impaired activation of the alpha-MSH receptor. To examine the involvement of SIK2 in the regulation of the melanogenesis switch in vivo, we prepared SIK2-knockout mice, and the Sik2-/- genotype was introduced into Ay/a mice. The resultant Sik2-/-; Ay/a mice had brown hair, indicating that SIK2 represses eumelanogenesis in mice.
- リンク情報
- ID情報
-
- DOI : 10.1111/j.1755-148X.2010.00760.x
- ISSN : 1755-1471
- PubMed ID : 20819186
- Web of Science ID : WOS:000282977800014