Glutamate metabolism is one of the central cellular pathways in Sulfolobus (http://www.genome.jp/dbget-bin/show_pathway?sso00251SSO2044) and is integrated with numerous other pathways such as glutathione metabolism, a major contributor to antioxidant protection.
Gangliosides, and particularly GM3 and GD3 are involved in regulation of numerous cellular pathways, such as migration, proliferation, senescence and apoptosis [41] [43] and ganglioside levels change over time in muscle cells, particularly during differentiation [44] [46].
So far, the possible relationship between GM3 synthesis and HIBM was never investigated, yet GM3 is a glycosphingolipid largely involved in differentiation of muscle cells [44] [46] and, more generally, in numerous cellular pathways, such as migration, proliferation, apoptosis or insulin sensitivity [42], [43].
Glycogen synthase kinase 3 β (GSK3 β) is a rate-limiting enzyme, which acts as a downstream regulatory switch for numerous signaling pathways such as insulin action, hepatic glycogen synthesis, and lipogenesis.
This intricate architecture is maintained by structures called cristae junctions (CJs) and contact sites (CSs) and has been shown to be essential for numerous mitochondrial pathways such as protein import, oxidative phosphorylation, and apoptosis (Freya and Mannellab, 2000; Vogel et al., 2006; Yang et al., 2012; Cogliati et al., 2013).
The mechanism of endocrine responsiveness in breast cancer is thought to be controlled by complex interactions between steroid hormones and numerous signaling pathways, such as growth factor signaling, which in turn most likely can be affected by different genetic alterations [ 42].
At present, numerous pathway components such as receptors, adapters, scaffolds and their interactions with ligands and other signaling proteins have been already characterized and, in some cases, reengineered.
Notably, GeneGo pathway analysis33 of these differentially expressed genes demonstrated that numerous immune response pathways such as PD-1, CTLA-4 checkpoints, T-cell receptor signaling, and several chemokine/chemotaxis factors were significantly (P < 0.05, fold change > 1.5, and FDR < 10%) enriched as a result of MEKi (Supplementary Fig. 10A; Supplementary Data 2).
Cell apoptosis is a tightly regulated process under the control of numerous signal transduction pathways, such as phosphatidylinositol 3-kinase (PI3K /AKT pathway.
