Identifier: R-HSA-9857590
Compartment:
nucleoplasm,
cytoplasm
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).