Browsing by Subject "Signaling"
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- PublicationOpen AccessA Side-by-Side comparison of wildtype and variant melanocortin 1 receptor signaling with emphasis on protection against oxidative damage to DNA.(MDPI, 2023-09-21) Cerdido, Sonia; Sánchez-Beltrán, José; Lambertos, Ana; Abrisqueta, Marta; Padilla, Lidia; Herraiz Serrano, Cecilia María; Jiménez-Cervantes, Celia; García-Borrón, José Carlos; Olivares, Conchi; Bioquímica y Biología Molecular B e InmunologíaCommon variants of the MC1R gene coding the α-melanocyte stimulating hormone receptor are associated with light skin, poor tanning, blond or red hair, and increased melanoma risk, due to pigment-dependent and -independent effects. This complex phenotype is usually attributed to impaired activation of cAMP signaling. However, several MC1R variants show significant residual coupling to cAMP and efficiently activate mitogenic extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling. Yet, residual signaling and the key actions of wildtype and variant MC1R have never been assessed under strictly comparable conditions in melanocytic cells of identical genetic background. We devised a strategy based on CRISPR-Cas9 knockout of endogenous MC1R in a human melanoma cell line wildtype for BRAF, NRAS and NF1, followed by reconstitution with epitope-labeled MC1R constructs, and functional analysis of clones expressing comparable levels of wildtype, R151C or D294H MC1R. The proliferation rate, shape, adhesion, motility and sensitivity to oxidative DNA damage were compared. The R151C and D294H RHC variants displayed impaired cAMP signaling, intracellular stability similar to the wildtype, triggered ERK1/2 activation as effectively as the wildtype, and afforded partial protection against oxidative DNA damage, although less efficiently than the wildtype. Therefore, common melanoma-associated MC1R variants display biased signaling and significant genoprotective activity.
- PublicationOpen AccessFibroblast growth factor receptors: multifactorial-contributors to tumor initiation and progression(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Feng, Shachuan; Zhou, Li; Collins Nice, Edouard; Huang, CanhuaFibroblast growth factor receptors (FGFRs), encoded by four genes (FGFR1, FGFR2, FGFR3, and FGFR4) are tightly associated with many biological processes such as organ development, cell proliferation and migration. Studies over the past decades have validated the pivotal roles FGFRs play in tumorigenesis due to the regulation of diverse tumorigenesis-related processes, including cell survival, proliferation, inflammation, metastasis and angiogenesis. Interestingly, FGFR mutations in somatic cells leading to tumorigenesis and those in germ cells leading to developmental disorders are identical, suggesting that FGFR mutations result in different diseases due to their spatio-temporal expression. Thus, discoveries in developmental biology may also be applicable to cancer. FGFRs regulate the expression and/or the activity of a myriad of molecules (e.g. matrix metalloproteinases (MMPs) and Snail) that are tightly linked to tumorigenesis by four main signaling pathways (RASMAPK, PI3K-AKT, PLCγ-PIP2, and STAT), as well as other minor branches. Epigenetic and genetic alteration of FGFR genes, including DNA methylation, histone remodeling, microRNA regulation, single nucleotide polymorphisms (SNPs), gene missense mutations, amplification, and fusion of FGFRs with other genes, which result in gain or loss of FGFR function, have been identified in many types of cancer. In this review, we focus in particular on recent advances in the relationship between FGFR disorders and tumorigenesis.
- PublicationOpen AccessGRP78, A chaperone with diverse roles beyond the endoplasmic reticulum(Murcia : F. Hernández, 2008) Quinones, Quintin J.; Ridder, Gustaaf G. de; Pizzo, Salvatore V.Glucose-regulated protein 78 (GRP78) is a well-characterized molecular chaperone that is ubiquitously expressed in mammalian cells. GRP78 is best known for binding to hydrophobic patches on nascent polypeptides within the endoplasmic reticulum (ER) and for its role in signaling the unfolded protein response. Structurally, GRP78 is highly conserved across species. The presence of GRP78 or a homologue in nearly every organism from bacteria to man, reflects the central roles it plays in cell survival. While the principal role of GRP78 as a molecular chaperone is a matter of continuing study, independent work demonstrates that like many other proteins with ancient origins, GRP78 plays more roles than originally appreciated. Studies have shown that GRP78 is expressed on the cell surface in many tissue types both in vitro and in vivo. Cell surface GRP78 is involved in transducing signals from ligands as disparate as activated a2-macroglobulin and antibodies. Plasmalemmar GRP78 also plays a role in viral entry of Coxsackie B, and Dengue Fever viruses. GRP78 disregulation is also implicated in atherosclerotic, thrombotic, and auto-immune disease. It is challenging to posit a hypothesis as to why an ER molecular chaperone, such as GRP78, plays such a variety of roles in cellular processes. An ancient and highly conserved protein such as GRP78, whose primary function is to bind to misfolded polypeptides, could be uniquely suited to bind a wide variety of ligands and thus, over time, could assume the wide variety of roles it now plays.
- PublicationOpen AccessHow does corporate altruism affect oligopolistic competition?(Elsevier, 2024-06) Candel Sánchez, Francisco; Perote Peña, Juan; Fundamentos del Análisis EconómicoThis paper examines firms' corporate social responsibility (CSR) competition in a duopoly model with product differentiation. Firms exhibit different degrees of altruism, which is a characteristic positively valued by consumers; however, as each firm's degree of altruism (type) is private information, using CSR activities to signal the types becomes an additional tool for competition. We analyze a game where firms first signal about their types and then compete in standard price competition. Consumers observe the firms' CSR activities and infer their degree of altruism. Firms then simultaneously set prices, and consumers purchase goods from one firm or the other. In equilibrium, CSR is determined by the consumers' valuation of corporate altruism and the degree of product differentiation. The model examines the interaction between these two determinants, finding that more competition in the market (less product differentiation) might be detrimental to CSR when consumers' concern about firms' altruism is high enough.
- PublicationOpen AccessIncentives for prosocial behavior under reputation persistence and policy lags(Springer, 2023-08) Candel Sánchez, Francisco; Perote Peña, Juan; Fundamentos del Análisis Económico
- PublicationOpen AccessIQGAP1: A microtubule-microfilament scaffolding protein with multiple roles in nerve cell development and synaptic plasticity(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Jausoro, Ignacio; Mestres, Iván; Remedi, Mónica; Sanchez, Mónica; Cáceres, AlfredoIn this article, we review our current understanding of the biology of IQ domain-containing GTPase-Activating Protein 1, IQGAP1, a scaffolding protein with multiple binding partners, which is widely expressed among different cell types, including neurons, and capable of linking Rho-GTPase signaling with cytosleletal elements and environmental cues. Interestingly, a series of recent studies suggest that IQGAP family members have an important role in neuronal development, synaptic plasticity and nervo system disorders involving alterations in spine density.
- PublicationOpen Accesslnterferons and cell growth control(Murcia : F. Hernández, 2000) Kalvakolanu, D.V.Cytokines modulate cell growth, differentiation, and immune defenses in the vertebrates. Interferons (IFNs) are a unique class of cytokines that stimulate antiviral, antitumor and antigen presentation by inducing the expression of several cellular genes. Recent studies have identified a novel gene regulatory pathway activated by IFNs, which serves as a paradigm for most cytokine signal transduction pathways. A number of genes induced by IFNs participate in cell growth regulation and apoptosis. These include novel tumor suppressor genes. Although discovered as IFN-regulated factors, deletions of these genes cause leukemias in experimental models and in human patients. Genetic approaches have identified several novel regulators of apoptosis. Studies on the mechanism of action of these growth regulatory molecules are not only useful in identifying novel targets for the development of therapeutics but also help understand the molecular basis for loss of cell growth control and resistance to IFNs. This review focuses on the functions and roles of IFN regulated factors in cell growth control and mechanisms of disruption of IFN action in cancer cells.
- PublicationOpen AccessPhysiological and pathological significance of the molecular cross-talk between autophagy and apoptosis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Oral, Ozlem; Akkoc, Yunus; Bayraktar, Oznur; Gozuacik, Devrimy. Autophagy and apoptosis are two important molecular mechanisms that maintain cellular homeostasis under stress conditions. Autophagy represents an intracellular mechanism responsible for turnover of organelles and long-lived proteins through a lysosome-dependent degradation pathway. Cell death signals or sustained stress might trigger programmed cell death pathways, and among them, apoptosis is the most extensively studied one. Recent studies indicate the presence of a complex interplay between autophagy and apoptosis. Physiological relevance of autophagyapoptosis crosstalk was mainly shown in vitro. However, in vivo consequences possibly exist both during health and disease. In this review, we will summarize the current knowledge about molecular mechanisms connecting autophagy and apoptosis, and about the significance of this crosstalk for human health.