2015
DOI: 10.1371/journal.pone.0143142
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LEF-1 Regulates Tyrosinase Gene Transcription In Vitro

Abstract: TYR, DCT and MITF are three important genes involved in maintaining the mature phenotype and producing melanin; they therefore participate in neural crest cell development into melanocytes. Previous studies have revealed that the Wnt signaling factor lymphoid enhancer-binding factor (LEF-1) can enhance DCT and MITF gene expression. However, whether LEF-1 also affects TYR gene expression remains unclear. In the present study, we found that LEF-1 regulated TYR transcription in vitro. LEF-1 overexpression increas… Show more

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Cited by 20 publications
(19 citation statements)
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References 47 publications
(49 reference statements)
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“…LEF1, which is activated by canonical Wnt signaling, physically interacts with MITF leading to synergistic activation of DCT expression, and this effect is augmented by the presence of β‐catenin (Yasumoto et al., ). A similar interaction was observed at the promoters of TYR and MITF itself, although in these cases, the presence of β‐catenin was required (Saito et al., ; Wang et al., ). Interestingly, TCF1, which is closely related to LEF1, also activated DCT expression in combination with β‐catenin, but did not exhibit synergistic activity with MITF (Yasumoto et al., ).…”
Section: Additional Mitf Cofactors and Collaboratorsmentioning
confidence: 61%
“…LEF1, which is activated by canonical Wnt signaling, physically interacts with MITF leading to synergistic activation of DCT expression, and this effect is augmented by the presence of β‐catenin (Yasumoto et al., ). A similar interaction was observed at the promoters of TYR and MITF itself, although in these cases, the presence of β‐catenin was required (Saito et al., ; Wang et al., ). Interestingly, TCF1, which is closely related to LEF1, also activated DCT expression in combination with β‐catenin, but did not exhibit synergistic activity with MITF (Yasumoto et al., ).…”
Section: Additional Mitf Cofactors and Collaboratorsmentioning
confidence: 61%
“…Since we did not see strong effects on MITF gene expression in all cell lines tested, we do not assume MITF to play a leading part in the observed effects. TYR was additionally identified as a direct target of LEF1 dependent gene transcription [ 68 ].…”
Section: Discussionmentioning
confidence: 99%
“…In our resistant melanoma cells the elevated levels of β-catenin did not cause an increase in activity of the canonical Wnt signaling pathway although the increase in β-catenin was also detectable on a nuclear level. Target gene expression like MITF ( Dorsky et al, 2000 , Widlund et al, 2002 ) and Tyrosinase ( Wang et al, 2015 ) was even reduced in the resistant cells. This is in accordance with a previously identified resistant subpopulation of chronically treated melanomas with low MITF expression ( Müller et al, 2014 ).…”
Section: Discussionmentioning
confidence: 99%