Gamma secretase inhibition impairs HCMV replication by reduction of immediate early gene expression at the transcriptional level.

Due to diverse pathogenic potentials, there is a growing need for anti-HCMV agents. In this study, we show that treatment with DAPT, a γ-secretase inhibitor (GSI), impairs HCMV replication as assessed by a progeny assay based on immunostaining. This effect is not limited to DAPT because other GSIs with different structures and distinct mechanisms of action also exhibit a similar level of inhibitory effects on HCMV viral production, indicating that γ-secretase activity is required for efficient HCMV replication.

YAP Enhances FGF2-Dependent Neural Stem Cell Proliferation by Induction of FGF Receptor Expression.

The Hippo signaling pathway regulates cell proliferation and organ growth, and its activation is mainly reflected by the phosphorylation levels of Yes-associated protein (YAP). In this study, we show that YAP facilitates embryonic neural stem cell proliferation by elevating their responsiveness to fibroblast growth factor 2 (FGF2), one of the major growth factors for neural stem cells, in vivo as well as in vitro. Western blot and quantitative real-time PCR analyses revealed that expression of the FGF receptors (FGFRs) to were greatly increased by YAP expression upon FGF2 treatment, followed by upregulation of the mitogen-activated protein kinase and protein kinase B signaling pathways.

PACT increases mammalian embryonic neural stem cell properties by facilitating activation of the notch signaling pathway.

The protein activator of protein kinase R (PKR) (PACT) is known to play important roles in PKR regulation and microRNA biogenesis. Based on the observation that PACT is specifically expressed in the ventricular zone (VZ) at the mid-neurogenic period, we examine the role of PACT in this embryonic neural stem cell niche. Here, we provide the first evidence that PACT increases neurosphere formation, as well as expression of Notch target genes and the neural stem cell marker Sox2 in primary neural stem cells in vitro.