Veronica Reghellin

• Università degli Studi di Milano-Bicocca

Mitochondria play essential metabolic functions in eukaryotes. Although their major role is the generation of energy in the form of ATP, they are also involved in maintenance of cellular redox state, conversion and biosynthesis of metabolites and signal transduction. Most mitochondrial functions are conserved in eukaryotic systems and mitochondrial...

Before anaphase onset, budding yeast cells must align the mitotic spindle parallel to the mother-bud axis to ensure proper chromosome segregation. The protein kinase Snf1/AMPK is a highly conserved energy sensor, essential for adaptation to glucose limitation and in response to cellular stresses. However, recent findings indicate that it plays impo...

In eukaryotes, nutrient availability and metabolism are coordinated by sensing mechanisms and signaling pathways, which influence a broad set of cellular functions such as transcription and metabolic pathways to match environmental conditions. In yeast, Protein Kinase A (PKA) is activated in the presence of high glucose concentrations, favoring fas...

The metabolism of proliferating cells shows common features even in evolutionary distant organisms such as mammals and yeasts, for example the requirement for anabolic processes under tight control of signaling pathways. Analysis of the rewiring of metabolism, which occurs following the dysregulation of signaling pathways, provides new knowledge ab...

The hepatitis C virus (HCV) nonstructural (NS) protein 5A is a multi-functional protein that plays a central role in viral replication and assembly. Antiviral agents directly targeting NS5A are currently in clinical development. Although the elucidation of the mechanism of action (MOA) of NS5A inhibitors has been the focus of intensive research, de...

HCV replicons harboring putative 4-anilino quinazoline resistance mutations retain sensitivity to inhibition by AL-9. Huh7.5 cells where transiently transfected with genotype 1b subgenomic replicons carrying mutation triplets reported to be associated to resistance to 4-anilino quinazolines (ET-FAG, ET-PPA or ET-DLD) or with the parental replicon (...

Effect of AL-9 on subcellular distribution of type III PI kinases. Cellular localization of PI4KIIIα (green), PI4KIIIβ (green) or NS5A (red) was analyzed by immunofluorescence in Huh7.5 or JFH-4A cells incubated for 4 hrs with 8 µM AL-9 or DMSO (control). Zoomed sections are indicated by a white square. No major effect of AL-9 on the localization o...

Synthetic pathway for compound AL-9. Reagents and conditions: (a) n-BuLi, dry THF, −78°C 1 h, 20°C 3 h, Bu3SnCl, −78°C 2 h, RT overnight; (b) Formamide, 155°C, 16 h; (c) SOCl2, dry DMF, reflux, 5 h, 4-morpholinoaniline, dry CH3CN, reflux, 16 h; (d) compound 1, bis(triphenylphosphine) palladium dichloride, dry THF, reflux; (e) HCl 2M, THF/H2O 1 ∶ 1,...

Chemical synthesis of compound AL-9. (DOC)

Construction and assays of HCV replicons harboring putative resistance mutations. (DOC)

4-anilino quinazolines have been identified as inhibitors of HCV replication. The target of this class of compounds was proposed to be the viral protein NS5A, although unequivocal proof has never been presented. A 4-anilino quinazoline moiety is often found in kinase inhibitors, leading us to formulate the hypothesis that the anti-HCV activity disp...

CK2 is a highly conserved protein kinase involved in different cellular processes, which shows a higher activity in actively proliferating mammalian cells and in various types of cancer and cancer cell lines. We recently demonstrated that CK2 activity is strongly influenced by growth rate in yeast cells as well. Here, we extend our previous finding...

CK2 is a highly conserved protein kinase controlling different cellular processes. It shows a higher activity in proliferating mammalian cells, in various types of cancer cell lines and tumors. The findings presented herein provide the first evidence of an in vivo modulation of CK2 activity, dependent on growth rate, in Saccharomyces cerevisiae. In...