Herpes simplex virus 1 (HSV-1) remodels nuclear membranes during virus egress. Although the UL31 and UL34 proteins control nucleocapsid transit in infected cells, the molecular interactions required for their function are unclear. Here we report that the ␥ 1 34.5 gene product of HSV-1 facilitates nucleocapsid release to the cytoplasm through bridging the UL31/UL34 complex, cellular p32, and protein kinase C. Unlike wild-type virus, an HSV mutant devoid of ␥ 1 34.5 or its amino terminus is crippled for viral growth and release. This is attributable to a defect in virus nuclear egress. In infected cells, wild-type virus recruits protein kinase C to the nuclear membrane and triggers its activation, whereas the ␥ 1 34.5 mutants fail to exert such an effect. Accordingly, the ␥ 1 34.5 mutants are unable to induce phosphorylation and reorganization of lamin A/C. When expressed in host cells ␥ 1 34.5 targets p32 and protein kinase C. Meanwhile, it communicates with the UL31/UL34 complex through UL31. Deletion of the amino terminus from ␥ 1 34.5 disrupts its activity. These results suggest that disintegration of the nuclear lamina mediated by ␥ 1 34.5 promotes HSV replication. IMPORTANCEHSV nuclear egress is a key step that determines the outcome of viral infection. While the nuclear egress complex mediates capsid transit across the nuclear membrane, the regulatory components are not clearly defined in virus-infected cells. We report that the ␥ 1 34.5 gene product, a virulence factor of HSV-1, facilitates nuclear egress cooperatively with cellular p32, protein kinase C, and the nuclear egress complex. This work highlights a viral mechanism that may contribute to the pathogenesis of HSV infection. Herpes simplex virus 1 (HSV-1) replicates and packages its DNA in the cell nucleus. Once assembled, the nucleocapsids traverse the nucleoplasm and cross the nuclear lamina. The capsids bud through the nuclear membranes in a two-step process called envelopment and de-envelopment (1). In this process, the nuclear egress complex, consisting of UL31 and UL34, mediates vesiculation of the inner nuclear membrane and results in enveloped virions in the perinuclear space. Primary virions fuse with the outer nuclear membrane, which releases the capsids to the cytoplasm for further maturation (2). Accumulating evidence suggests that additional proteins, including Us3, ICP22, UL47, gB, and gH, coordinate with the UL31/34 complex to facilitate nuclear egress in infected cells (3-6).The nuclear lamina is a dense meshwork underlying the inner nuclear membrane (7). It is composed primarily of type V intermediate filament proteins, lamin A/C and lamin B. Besides providing structural support to the nucleus, the nuclear lamina potentially presents a barrier to the transit of virus capsids. A number of studies suggest that herpesviruses alter the nuclear lamina to promote nuclear egress (8-11). For example, HSV-1 activates protein kinase C (PKC) isoforms and induces phosphorylation of lamin B, which is dependent on the UL31/UL34 complex (1...
Copper chaperone for superoxide dismutase (CCS) is a critical component of oxidation–reduction system and functions as a potential tumor promoter in several cancers. However, the function and clinical significance of CCS in breast cancer remain unclear. Here, we found CCS was highly expressed in breast cancer, where it promoted breast cancer cell proliferation and migration. Suppression of CCS expression was sufficient to attenuate the phosphorylation level of ERK1/2 and increase the accumulation of reactive oxygen species (ROS). Mechanistically, we found that knockdown of CCS decreases the activity of ERK1/2 mediated by the accumulation of ROS, which leads to the inhibition of cell proliferation and migration. In summary, these results indicated that CCS promotes the growth and migration of breast cancer cells via regulating the ERK1/2 activity mediated by ROS.
Abstract:Measuring the impact of livestock grazing on grassland above-ground net primary production (ANPP) is essential for grass yield estimation and pasture management. However, since there is a lack of accurate and repeatable techniques to obtain the details of grazing locations and stocking rates at the regional scale, it is an extremely challenging task to study the influence of regional grazing on the grassland ANPP. Taking Zoige County as a case, this paper proposes an approach to quantify the spatial and temporal variation of grazing intensity and grazing period through time-series remote sensing data, simulated grassland ANPP through the denitrification and decomposition (DNDC) model, and then explores the impact of grazing on grassland ANPP. The result showed that the model-estimated ANPP while considering grazing had a significant relationship with the field-observed ANPP, with the coefficient of determination (R 2 ) of 0.75, root mean square error (RMSE) of 122.86 kgC/ha, and average relative error (RE) of 8.77%. On the contrary, if grazing activity was not considered in simulation, a large uncertainty was found when the model-estimated ANPP was compared with the field observation, showing R 2 of 0.4, RMSE of 211.51 kgC/ha, and average RE of 32.5%. For the whole area of Zoige County in 2012, the statistics of the estimation showed that the total regional ANPP was up to 3.815ˆ10 5 tC, while the total regional ANPP, without considering grazing, would be overestimated by 44.4%, up to 5.51ˆ10 5 tC. This indicates that the grazing parameters derived in this study could effectively improve the accuracy of ANPP simulation results. Therefore, it is feasible to combine time-series remote sensing data with the process model to simulate the grazing effects on grassland ANPP. However, some issues, such as selecting proper remote sensing data, improving the quality of model input parameters, collecting more field data, and exploring the data assimilation approaches, still should be considered in the future work.
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