We therefore investigated the potential role of CK2 phosphorylation upon E1B-55K during adenoviral infection. A phosphonegative E1B-55K mutant showed severely reduced virus progeny production, although viral early, late, and structural protein levels and viral DNA replication were not obviously affected. Binding studies revealed an interaction between the CK2 alpha catalytic subunit and wild-type E1B-55K, which is severely impaired in the phosphonegative El B mutant. In addition, in situ the alpha-catalytic subunit is redistributed into ring-like structures surrounding E1B-55K nuclear areas and distinct cytoplasmic accumulations, where a significant amount of CK2
alpha colocalizes with E1B-55K. Furthermore, in in vitro phosphorylation assays, PCI-32765 nmr wild-type E1B-55K glutathione S-transferase fusion proteins were readily phosphorylated by the CK2 alpha subunit but inefficiently phosphorylated click here by the CK2 holoenzyme. Addition of the CK2-specific inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) to infected cells confirmed that CK2 alpha binding to E1B-55K is necessary for efficient phosphorylation of E1B-55K. In summary, our data show that CK2 alpha interacts with and phosphorylates HAdV5 E1B-55K at residues S490/491 and T495
and that these posttranslational modifications are essential for E1B-55K lytic functions.”
“A recent ‘mega-analysis’ combining genome-wide Fludarabine concentration association study data from over 40 000 individuals identified novel genetic loci associated with schizophrenia (SCZ) at genome-wide significance level. The strongest finding was a locus within an intron of a putative primary transcript for microRNA MIR137. In the current study, we examine the impact of variation at this locus (rs1625579, G/T; where T is the common and presumed risk
allele) on brain activation during a sentence completion task that differentiates individuals with SCZ, bipolar disorder (BD), and their relatives from controls. We examined three groups of individuals performing a sentence completion paradigm: (i) individuals at high genetic risk of SCZ (n = 44), (ii) individuals at high genetic risk of BD (n = 90), and (iii) healthy controls (n = 81) in order to test the hypothesis that genotype at rs1625579 would influence brain activation. Genotype groups were assigned as ‘RISK -’ for GT and GG individuals, and ‘RISK +’ for TT homozygotes. The main effect of genotype was significantly greater activation in the RISK – individuals in the posterior right medial frontal gyrus, BA 6. There was also a significant genotype*group interaction in the left amygdala and left pre/postcentral gyrus. This was due to differences between the controls (where individuals with the RISK – genotype showed greater activation than RISK + subjects) and the SCZ high-risk group, where the opposite genotype effect was seen.