Inverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1.
The pink-eyed dilution protein (p) plays a pivotal role in the synthesis of eumelanin. In its absence, critical melanosomal proteins fail to traffic to the melanosome. Pink-eyed dilution gene (P) mutations are the most common cause of tyrosinase-positive oculocutaneous albinism worldwide. Thus, reports that bafilomycin A1 was able to induce synthesis of melanin in tyrosinase-positive melanomas led us to test the drug on p-null murine melanocytes. We found that in melanocytes lacking p, bafilomycin A1 was able to induce melanin synthesis. These cells, once transfected with an expression vector encoding an epitope-tagged p transcript, failed to respond to the drug. The increase in melanin synthesis is accompanied by a reduction in tyrosinase protein cleavage and secretion with subsequent accumulation within the melanocyte. Bafilomycin A1 has also been reported to induce pigmentation of normal Caucasian melanocytes. Based on these data we hypothesize that p may serve as a key control point at which ethnic skin color variation is determined.
Manga
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The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, NY 10016, USA.
Orlow
S J
SJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002352:Carrier Proteins; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018942:Macrolides; D008543:Melanins / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012880:Skin Pigmentation / Q000502:physiology*
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D018942:Macrolides; D008543:Melanins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C076239:P protein, mouse; C036978:concanamycin A; C040929:bafilomycin A1; D014442:Monophenol Monooxygenase