No abstract

Dentatorubral-pallidoluysian atrophy is a progressive neurodegenerative disease caused by the expansion of a polyglutamine repeats within the Atrophin-1 protein. The in vivo function of Atrophin-1 is unknown. We have characterized a Drosophila gene encoding an Atrophin family protein. Analysis of mutant phenotypes indicates that Drosophila Atrophin is required in diverse developmental processes including early embryonic patterning. Drosophila Atrophin genetically interacts with the transcription repressor even-skipped and is required for its repressive function in vivo. Drosophila Atrophin directly binds to Even-skipped in vitro. Furthermore, both human Atrophin-1 and Drosophila Atrophin repress transcription in vivo when tethered to DNA, and poly-Q expansion in Atrophin-1 reduces this repressive activity. We propose that Atrophin proteins function as versatile transcriptional corepressors and discuss a model that deregulation of transcription may contribute to the pathogenesis of neurodegeneration.

No abstract

Interferon-stimulated genes (ISGs) are a group of gene products that coordinately combat pathogen invasions, in particular viral infections. Transcription of ISGs occurs rapidly upon pathogen invasion, and this is classically provoked via activation of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway, mainly by interferons (IFNs). However, a plethora of recent studies have reported a variety of non-canonical mechanisms regulating ISG transcription. These new studies are extremely important for understanding the quantitative and temporal differences in ISG transcription under specific circumstances. Because these canonical and non-canonical regulatory mechanisms are essential for defining the nature of host defense and associated detrimental proinflammatory effects, we comprehensively review the state of this rapidly evolving field and the clinical implications of recently acquired knowledge in this respect.