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Autophagy. 2019 Feb;15(2):366-367. doi: 10.1080/15548627.2018.1522911. Epub 2018 Sep 22.

Darkening with UVRAG.

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a Department of Molecular Microbiology and Immunology , University of Southern California , Los Angeles , CA , USA.


Ultraviolet radiation (UVR)-induced skin pigmentation, afforded by the dark organelles termed melanosomes, accounts for the first-line protection against environmental UVR that increases the risk of developing skin cancers including melanoma. We have recently discovered that UVRAG, originally identified as a BECN1-binding macroautophagy/autophagy protein, appears to have a specialized function in melanosome biogenesis beyond autophagy through its interaction with the biogenesis of lysosome-related organelles complex 1 (BLOC-1). This melanogenic function of UVRAG is controlled by the melanocyte-specific transcription factor MITF as a downstream effector of the α-melanocyte-stimulating hormone (α-MSH)-cAMP signaling in the suntan response, which is compromised in BRAF mutant melanoma. Thus we propose a new mode of UVRAG activity and regulation in melanocyte biology that may affect melanoma predisposition.


Autophagy; BLOC-1; BRAF; UVRAG; melanosome

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