header logo image header logo text
Downloads Login
Research
General Information
ZIRC
ZFIN ID: ZDB-PUB-180801-5
Central role of autophagic UVRAG in melanogenesis and the suntan response
Yang, Y., Jang, G.B., Yang, X., Wang, Q., He, S., Li, S., Quach, C., Zhao, S., Li, F., Yuan, Z., Lee, H.R., Zhong, H., Liang, C.
Date: 2018
Source: Proceedings of the National Academy of Sciences of the United States of America   115(33): E7728-E7737 (Journal)
Registered Authors: Yang, Xuanjun, Zhong, Hanbing
Keywords: BLOC-1, BRAF, MITF, UVRAG, melanosome
MeSH Terms:
  • Animals
  • HEK293 Cells
  • Humans
  • Melanins/biosynthesis*
  • Melanins/genetics
  • Melanoma/genetics
  • Melanoma/metabolism
  • Melanosomes/genetics
  • Melanosomes/metabolism*
  • Microphthalmia-Associated Transcription Factor/genetics
  • Microphthalmia-Associated Transcription Factor/metabolism
  • Proto-Oncogene Proteins B-raf/genetics
  • Proto-Oncogene Proteins B-raf/metabolism
  • Skin Pigmentation/radiation effects*
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Ultraviolet Rays*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 30061422 Full text @ Proc. Natl. Acad. Sci. USA
FIGURES
ABSTRACT
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 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 α-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.
ADDITIONAL INFORMATION