MITF-M dimer binds GMPR gene

Stable Identifier
R-HSA-9857578
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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MITF-M controls the expression of the guanosine monophosphate reductase gene GMPR as assessed by ChIP in human melanoma and normal human melanocyte cells (Bianchi-Smiraglia et al, 2017; Strub et al, 2011). GMPR expression is downregulated in melanoma cell lines in a MITF-dependent manner. Decreased expression of GMPR causes an elevation of cellular GTP levels, an increase in formation of active RAC:GTP complexes and an increased invasive potential (Bianchi-Smiraglia et al, 2017; Wawrzyniak et al, 2013; reviewed in Goding and Arnheiter, 2019).
Microarray analysis identified GMPR as a MITF-dependent target gene (Hoek et al, 2008). Promoter analysis of the GMPR gene in human and mouse reveals several conserved E- and M-box motifs in the distal and proximal regions. Promoter analysis with a 250 bp region containing the three most proximal sites, including the completely conserved Box 7, drives MITF-dependent expression of a reporter gene, and mutation of the Box 7 M-box site abrogates this expression, consistent with the ChIP results identifying MITF as a direct regulator of GMPR gene expression (Bianchi-Smiraglia et al, 2017; Strub et al, 2011).
Literature References
PubMed ID Title Journal Year
19067971 Novel MITF targets identified using a two-step DNA microarray strategy

Eichhoff, OM, Bergsteinsdóttir, K, Schlegel, NC, Einarsson, SO, Widmer, DS, Praetorius, C, Steingrímsson, E, Dummer, R, Schepsky, A, Valgeirsdottir, S, Hoek, KS

Pigment Cell Melanoma Res 2008
21258399 Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma

Ye, T, Cormont, M, Keime, C, Kobi, D, Davidson, I, Le Gras, S, Giuliano, S, Bonet, C, Bertolotto, C, Ballotti, R, Strub, T

Oncogene 2011
27181209 Microphthalmia-associated transcription factor suppresses invasion by reducing intracellular GTP pools

Kozlova, NI, Jowdy, P, Moparthy, S, Battaglia, S, Ackroyd, JJ, Lipchick, BC, Foley, CE, Marvin, EK, Shewach, DS, Bianchi-Smiraglia, A, Bagati, A, Fink, EE, Kolesnikova, M, Paul-Rosner, LM, Nikiforov, MA, Wawrzyniak, JA, Bshara, W, Berman, AE

Oncogene 2017
31123060 MITF-the first 25 years

Arnheiter, H, Goding, CR

Genes Dev 2019
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