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dc.contributor.authorA. Newton, Richard
dc.contributor.authorCook, A.
dc.contributor.authorW. Roberts, Donald
dc.contributor.authorHelen Leonard, J.
dc.contributor.authorSturm, Richard A.
dc.date.accessioned2017-05-03T16:57:50Z
dc.date.available2017-05-03T16:57:50Z
dc.date.issued2007
dc.date.modified2009-07-29T06:08:43Z
dc.identifier.issn0022202X
dc.identifier.doi10.1038/sj.jid.5700840
dc.identifier.urihttp://hdl.handle.net/10072/24918
dc.description.abstractUpregulation of microphthalmia-associated transcription factor (MITF) expression has been proposed to mediate melanogenesis stimulated by cAMP, whereas downregulation of MITF has been suggested to underlie the depigmentary effects of resveratrol, a promising chemotherapeutic found in red wine. We have assessed the contribution of MITF to pigmentation regulation by treating primary cultures of normal human melanocytes with the adenylate cyclase activator forskolin and/or resveratrol, then quantifying mRNA and protein levels for MITF, tyrosinase, tyrosinase-related protein-1, and dopachrome tautomerase (DCT). The inhibition of tyrosinase activity by resveratrol was not due to alterations in MITF, but instead was explained by both direct tyrosinase inhibition and a post-transcriptional effect that reduced the amount of fully processed tyrosinase. Glycosidase digestion revealed that the basis for the tyrosinase decrease was the retention of an immature form in the ER and subsequent loss of the mature, Golgi-processed enzyme. Elevation of intracellular cAMP by forskolin markedly increased protein levels for MITF, tyrosinase and DCT, however there was no concomitant increase in tyrosinase or DCT mRNA. This indicated that elevated levels of MITF were not sufficient to promote transcription of these melanogenic genes and that the increase in their protein abundance appeared to be predominantly mediated through post-transcriptional processing events.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.publisher.urihttp://www.nature.com/jid/
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom2216
dc.relation.ispartofpageto2227
dc.relation.ispartofissue9
dc.relation.ispartofjournalJournal of Investigative Dermatology
dc.relation.ispartofvolume127
dc.rights.retentionY
dc.subject.fieldofresearchEnzymes
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode060107
dc.subject.fieldofresearchcode1103
dc.subject.fieldofresearchcode1112
dc.titlePost-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2007
gro.hasfulltextNo Full Text
gro.griffith.authorCook, Anthony


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