LEF1, CTNNB1 and MITF-M bind the MITF promoter

Stable Identifier
R-HSA-9824598
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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LEF1, CTNNB1 and MITF-M bind the MITF promoter
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WNT3A and WNT1 promote melanocyte lineage development, expansion of melanocytes from neural crest cells and expression of the melanocyte-specific isoform of MITF (Ikeya et al, 1997; Dorsky et al, 1998; Dunn et al, 2005; Takeda et al, 2000). In response to WNT3A, LEF1 and CTNNB1 (beta catenin) bind to 3 LEF1 elements in the M-promoter of MITF to drive expression, as assessed by EMSA, ChIP and reporter gene assays. Mutation of the LEF1 binding site abolishes both the interaction of LEF1 with the promoter and the activation of MITF-M expression (Takeda et al, 2000; Dorsky et al, 2000; Widlund et al, 2002).
MITF protein has been shown to interact with LEF1 by co-immunoprecipitation, and MITF-M stimulates its own expression in a manner that is independent of its DNA binding (Saito et al, 2002, Wang et al 2018). MITF also interacts directly with CTNNB1 (beta-catenin) at MITF-dependent promoters and may redirect CTNNB1 away from canonical WNT transcriptional targets during melanocyte development and melanoma progression (Schepsky et al, 2006). MITF-responsive transcription is dose-dependent, with MITF-M synergizing with LEF1 at lower concentrations to stimulate its own transcription, but inhibiting expression at higher doses.
WNT-, beta-catenin- and LEF1-driven MITF expression is also seen in melanoma cell lines, where MITF contributes to proliferation and survival (Widlund et al, 2002).
Literature References
PubMed ID Title Journal Year
12048204 Melanocyte-specific microphthalmia-associated transcription factor isoform activates its own gene promoter through physical interaction with lymphoid-enhancing factor 1

Saito, H, Yasumoto, K, Takeda, K, Takahashi, K, Fukuzaki, A, Orikasa, S, Shibahara, S

J Biol Chem 2002
29531335 Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations

Wang, XP, Liu, YL, Mei, LY, He, CF, Niu, ZJ, Sun, J, Zhao, YL, Feng, Y, Zhang, H

J Hum Genet 2018
9353119 Wnt signalling required for expansion of neural crest and CNS progenitors

Ikeya, M, Lee, SM, Johnson, JE, McMahon, AP, Takada, S

Nature 1997
17000761 The microphthalmia-associated transcription factor Mitf interacts with beta-catenin to determine target gene expression

Schepsky, A, Bruser, K, Gunnarsson, GJ, Goodall, J, Hallsson, JH, Goding, CR, Steingrímsson, E, Hecht, A

Mol Cell Biol 2006
12235125 Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor

Widlund, HR, Horstmann, MA, Price, ER, Cui, J, Lessnick, SL, Wu, M, He, X, Fisher, DE

J Cell Biol 2002
10652270 Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway

Dorsky, RI, Raible, DW, Moon, RT

Genes Dev 2000
15892713 WNT1 and WNT3a promote expansion of melanocytes through distinct modes of action

Dunn, KJ, Brady, M, Ochsenbauer-Jambor, C, Snyder, S, Incao, A, Pavan, WJ

Pigment Cell Res 2005
10747853 Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a

Takeda, K, Yasumoto, K, Takada, R, Takada, S, Watanabe, K, Udono, T, Saito, H, Takahashi, K, Shibahara, S

J Biol Chem 2000
Participants
Input
Output
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as an event of
This event is regulated
Positively by
Regulator
N4GlycoAsn-PalmS WNT3A [extracellular region] (Homo sapiens)
Authored
Rothfels, K  (2023-01-26)
Reviewed
Arnheiter, H  (2024-02-26)
de la Serna, IL  (2024-05-21)
Vu, HN  (2024-11-05)
Steingrímsson, E  (2024-11-05)
Created
Rothfels, K  (2023-01-20)
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