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Central role of autophagic UVRAG in melanogenesis and the suntan response.

ABSTRACT: UV-induced cell pigmentation represents an important mechanism against skin cancers. Sun-exposed skin secretes ?-MSH, which induces the lineage-specific transcriptional factor MITF and activates melanogenesis in melanocytes. Here, we show that the autophagic tumor suppressor UVRAG plays an integral role in melanogenesis by interaction with the biogenesis of lysosome-related organelles complex 1 (BLOC-1). This interaction is required for BLOC-1 stability and for BLOC-1-mediated cargo sorting and delivery to melanosomes. Absence of UVRAG dispersed BLOC-1 distribution and activity, resulting in impaired melanogenesis in vitro and defective melanocyte development in zebrafish in vivo. Furthermore, our results establish UVRAG as an important effector for melanocytes' response to ?-MSH signaling as a direct target of MITF and reveal the molecular basis underlying the association between oncogenic BRAF and compromised UV protection in melanoma.

SUBMITTER: Yang Y 

PROVIDER: S-EPMC6099899 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Central role of autophagic UVRAG in melanogenesis and the suntan response.

Yang Yongfei Y   Jang Gyu-Beom GB   Yang Xuanjun X   Wang Qiaoxiu Q   He Shanshan S   Li Shun S   Quach Christine C   Zhao Shihui S   Li Fan F   Yuan Zengqiang Z   Lee Hye-Ra HR   Zhong Hanbing H   Liang Chengyu C  

Proceedings of the National Academy of Sciences of the United States of America 20180730 33

UV-induced cell pigmentation represents an important mechanism against skin cancers. Sun-exposed skin secretes α-MSH, which induces the lineage-specific transcriptional factor MITF and activates melanogenesis in melanocytes. Here, we show that the autophagic tumor suppressor UVRAG plays an integral role in melanogenesis by interaction with the biogenesis of lysosome-related organelles complex 1 (BLOC-1). This interaction is required for BLOC-1 stability and for BLOC-1-mediated cargo sorting and  ...[more]