MITF-M-dependent GMPR expression

Stable Identifier
R-HSA-9857590
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, cytoplasm
ReviewStatus
5/5
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MITF-M-dependent GMPR expression
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GMPR encodes guanosine monophosphate reductase, a tetrameric enzyme that catalyzes the deamination of GMP to inosine monophosphate (IMP). IMP can be converted into AMP or, through the action of inosine monophosphate dehydrogenase enzymes, can be converted back to GMP. In this way, IMP is a branch point in purine biosynthesis pathways (reviewed in D'Angiolella et al, 2014).
Expression of GMPR is decreased in a number of melanoma cell lines, resulting in dysregulation of GMP and AMP levels. These cells show elevated levels of GTP relative to normal cells (Wawrzyniak et al, 2013; Bianchi-Smirglia et al, 2017; reviewed in D'Angiolella et al, 2014). MITF expression is also decreased in melanoma cells and low MITF levels are correlated with increased invasive potential (Carreira et al, 2006; Giuliano et al, 2010; reviewed in Vachtenheim and Ondrusova, 2015).
GMPR is a direct target of MITF-M in melanoma and normal human melanocytes (Bianchi-Smiraglia et al, 2017; Strub et al, 2011; Hoek et al, 2008). Abrogation of MITF-M dependent GMPR expression results in elevated GTP levels, and increase in the formation of active, GTP-bound RAC1, RHOA and RHOC complexes, increased formation of invadopodia and increased invasive potential (Bianchi-Smiraglia et al, 2017; reviewed in D'Angiolella et al, 2014; Goding and Arnheiter, 2019).
Literature References
PubMed ID Title Journal Year
17182868 Mitf regulation of Dia1 controls melanoma proliferation and invasiveness

Carreira, S, Goodall, J, Denat, L, Rodriguez, M, Nuciforo, P, Hoek, KS, Testori, A, Larue, L, Goding, CR

Genes Dev 2006
19067971 Novel MITF targets identified using a two-step DNA microarray strategy

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

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

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

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

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

Oncogene 2017
24387760 Beyond survival: fine-tuning GTP production to boost melanoma invasion

D'Angiolella, V

Pigment Cell Melanoma Res 2014
31123060 MITF-the first 25 years

Goding, CR, Arnheiter, H

Genes Dev 2019
24139804 A purine nucleotide biosynthesis enzyme guanosine monophosphate reductase is a suppressor of melanoma invasion

Wawrzyniak, JA, Bianchi-Smiraglia, A, Bshara, W, Mannava, S, Ackroyd, J, Bagati, A, Omilian, AR, Im, M, Fedtsova, N, Miecznikowski, JC, Moparthy, KC, Zucker, SN, Zhu, Q, Kozlova, NI, Berman, AE, Hoek, KS, Gudkov, AV, Shewach, DS, Morrison, CD, Nikiforov, MA

Cell Rep 2013
25866058 Microphthalmia-associated transcription factor expression levels in melanoma cells contribute to cell invasion and proliferation

Vachtenheim, J, Ondrušová, L

Exp Dermatol 2015
20388797 Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas

Giuliano, S, Cheli, Y, Ohanna, M, Bonet, C, Beuret, L, Bille, K, Loubat, A, Hofman, V, Hofman, P, Ponzio, G, Bahadoran, P, Ballotti, R, Bertolotto, C

Cancer Res 2010
Participants
Input
Output
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as an event of
This event is regulated
Positively by
Regulator
MITF-M dimer:GMPR gene [nucleoplasm] (Homo sapiens)
Active Unit
MITF-M dimer [nucleoplasm]
Authored
Rothfels, K  (2023-12-21)
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  (2024-01-07)
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