RESUMEN
Adenoviruses are a group of double-stranded DNA viruses that can mainly cause respiratory, gastrointestinal, and eye infections in humans. In addition, adenoviruses are employed as vector vaccines for combatting viral infections, including SARS-CoV-2, and serve as excellent gene therapy vectors. These viruses have the ability to modulate the host cell machinery to their advantage and trigger significant restructuring of the nuclei of infected cells through the activity of viral proteins. One of those, the adenovirus DNA-binding protein (DBP), is a multifunctional non-structural protein that is integral to the reorganization processes. DBP is encoded in the E2A transcriptional unit and is highly abundant in infected cells. Its activity is unequivocally linked to the formation, structure, and integrity of virus-induced replication compartments, molecular hubs for the regulation of viral processes, and control of the infected cell. DBP also plays key roles in viral DNA replication, transcription, viral gene expression, and even host range specificity. Notably, post-translational modifications of DBP, such as SUMOylation and extensive phosphorylation, regulate its biological functions. DBP was first investigated in the 1970s, pioneering research on viral DNA-binding proteins. In this literature review, we provide an overview of DBP and specifically summarize key findings related to its complex structure, diverse functions, and significant role in the context of viral replication. Finally, we address novel insights and perspectives for future research.
Asunto(s)
Adenoviridae , Replicación del ADN , Proteínas de Unión al ADN , Proteínas Virales , Humanos , Adenoviridae/fisiología , Adenovirus Humanos/fisiología , ADN Viral/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismo , Replicación ViralRESUMEN
The multifunctional adenovirus E1B-55K oncoprotein can induce cell transformation in conjunction with adenovirus E1A gene products. Previous data from transient expression studies and in vitro experiments suggest that these growth-promoting activities correlate with E1B-55K-mediated transcriptional repression of p53-targeted genes. Here, we analyzed genome-wide occupancies and transcriptional consequences of species C5 and A12 E1B-55Ks in transformed mammalian cells by combinatory ChIP and RNA-seq analyses. E1B-55K-mediated repression correlates with tethering of the viral oncoprotein to p53-dependent promoters via DNA-bound p53. Moreover, we found that E1B-55K also interacts with and represses transcription of numerous p53-independent genes through interactions with transcription factors that play central roles in cancer and stress signaling. Our results demonstrate that E1B-55K oncoproteins function as promiscuous transcriptional repressors of both p53-dependent and -independent genes and further support the model that manipulation of cellular transcription is central to adenovirus-induced cell transformation and oncogenesis.
Asunto(s)
Adenovirus Humanos , Proteínas Oncogénicas Virales , Animales , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Adenovirus Humanos/genética , Adenovirus Humanos/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas E1B de Adenovirus/genética , Proteínas E1B de Adenovirus/metabolismo , Transformación Celular Neoplásica/genética , Adenoviridae/genética , Adenoviridae/metabolismo , Proteínas Oncogénicas Virales/metabolismo , ADN , Mamíferos/genéticaRESUMEN
Phenotypic plasticity is the ability of a genotype to produce different phenotypes depending on the environment. It has an influence on the adaptive potential to environmental change and the capability to adapt locally. Adaptation to environmental change happens at the population level, thereby contributing to genotypic and phenotypic variation within a species. Predation is an important ecological factor structuring communities and maintaining species diversity. Prey developed different strategies to reduce their vulnerability to predators by changing their behaviour, their morphology or their life history. Predator-induced life history responses in Daphnia have been investigated for decades, but intra-and inter-population variability was rarely addressed explicitly. We addressed this issue by conducting a common garden experiment with 24 clonal lines of European Daphnia galeata originating from four populations, each represented by six clonal lines. We recorded life history traits in the absence and presence of fish kairomones. Additionally, we looked at the shape of experimental individuals by conducting a geometric morphometric analysis, thus assessing predator-induced morphometric changes. Our data revealed high intraspecific phenotypic variation within and between four D. galeata populations, the potential to locally adapt to a vertebrate predator regime as well as an effect of the fish kairomones on morphology of D. galeata.
RESUMEN
Ca2+ signaling in astrocytes is considered to be mainly mediated by metabotropic receptors linked to intracellular Ca2+ release. However, recent studies demonstrate a significant contribution of Ca2+ influx to spontaneous and evoked Ca2+ signaling in astrocytes, suggesting that Ca2+ influx might account for astrocytic Ca2+ signaling to a greater extent than previously thought. Here, we investigated AMPA-evoked Ca2+ influx into olfactory bulb astrocytes in mouse brain slices using Fluo-4 and GCaMP6s, respectively. Bath application of AMPA evoked Ca2+ transients in periglomerular astrocytes that persisted after neuronal transmitter release was inhibited by tetrodotoxin and bafilomycin A1. Withdrawal of external Ca2+ suppressed AMPA-evoked Ca2+ transients, whereas depletion of Ca2+ stores had no effect. Both Ca2+ transients and inward currents induced by AMPA receptor activation were partly reduced by Naspm, a blocker of Ca2+-permeable AMPA receptors lacking the GluA2 subunit. Antibody staining revealed a strong expression of GluA1 and GluA4 and a weak expression of GluA2 in periglomerular astrocytes. Our results indicate that Naspm-sensitive, Ca2+-permeable AMPA receptors contribute to Ca2+ signaling in periglomerular astrocytes in the olfactory bulb.