18 research outputs found
Inhibition of MLC Phosphorylation Restricts Replication of Influenza VirusâA Mechanism of Action for Anti-Influenza Agents
Influenza A viruses are a severe threat worldwide, causing large epidemics that kill thousands every year. Prevention of influenza infection is complicated by continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK and protein kinase C inhibitors; however, the downstream effectors of these pathways have not been determined. In this study, we identified a common mechanism for the inhibitory effects of a significant group of anti-influenza agents. Our studies showed that influenza infection activates a series of signaling pathways that converge to induce myosin light chain (MLC) phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C, and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation leads to the inhibition of influenza proliferation. In contrast, the induction of MLC phosphorylation enhances influenza proliferation, as does activation of the HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC phosphorylation. Additionally, in intracellular trafficking studies, we found that the nuclear export of influenza ribonucleoprotein depends on MLC phosphorylation. Our studies provide evidence that modulation of MLC phosphorylation is an underlying mechanism for the inhibitory effects of many anti-influenza compounds
Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer
The incidence of thyroid cancers is increasing worldwide. Some
somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene
translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with
the development of thyroid cancer. In our study, we analyzed these
genetic alterations in 394 thyroid tissue samples (197 papillary
carcinomas and 197 healthy). The somatic mutations and
translocations were detected by Light Cycler melting method and
Real-Time Polymerase Chain Reaction techniques, respectively. In
tumorous samples, 86 BRAF (44.2 %), 5 NRAS (3.1 %), 2 HRAS (1.0 %)
and 1 KRAS (0.5 %) mutations were found, as well as 9 RET/PTC1 (4.6
%) and 1 RET/PTC3 (0.5 %) translocations. No genetic alteration was
seen in the non tumorous control thyroid tissues. No correlation
was detected between the genetic variants and the pathological
subtypes of papillary cancer as well as the severity of the
disease. Our results are only partly concordant with the data found
in the literature
p66Shcâa longevity redox protein in human prostate cancer progression and metastasis
p66Shc, a 66 kDa proto-oncogene Src homologous-collagen homologue (Shc) adaptor protein, is classically known in mediating receptor tyrosine kinase signaling and recently identified as a sensor to oxidative stress-induced apoptosis and as a longevity protein in mammals. The expression of p66Shc is decreased in mice and increased in human fibroblasts upon aging and in aging-related diseases, including prostate cancer. p66Shc protein level correlates with the proliferation of several carcinoma cells and can be regulated by steroid hormones. Recent advances point that p66Shc protein plays a role in mediating cross-talk between steroid hormones and redox signals by serving as a common convergence point in signaling pathways on cell proliferation and apoptosis. This article first reviews the unique function of p66Shc protein in regulating oxidative stress-induced apoptosis. Subsequently, we discuss its novel role in androgen-regulated prostate cancer cell proliferation and metastasis and the mechanism by which it mediates androgen action via the redox signaling pathway. The data together indicate that p66Shc might be a useful biomarker for the prognosis of prostate cancer and serve as an effective target for its cancer treatment