No description available.

No description available.

No description available.

Influenza A virus (family Orthomyxoviridae) is one of the most important human pathogens, causing annual epidemics with significant worldwide mortality, and sporadic but potentially devastating pandemics. The influenza A viral genome encodes 14 proteins and consists of 8 segments of negative-stranded RNA. During infection, the virus exploits the host cell signaling machinery to ensure efficient replication. The PI3K/Akt and Ras/ERK are two of the signaling cascades that are induced for virus survival. Influenza A virus replicates in the nucleus, hence the newly synthesized RNPs must be exported from the nucleus and exported to the cell membrane. Although the detailed mechanism of vRNP nuclear export is not yet fully elucidated, several studies on this process have begun to emerge. Influenza A virus nucleoprotein nuclear export is CRM1-dependent. Ran-binding protein 3 (RanBP3) is a Ran-interacting protein that is best known for its role as a cofactor of CRM1-mediated cargo nuclear export. In this study, we investigated the role of RanBP3 during the influenza A virus life cycle. We found that RanBP3 was phosphorylated at Ser58 in early and late phases of infection. Knockdown of RanBP3 expression led to a vRNP nuclear retention, suggesting that RanBP3 is involved in vRNP nuclear export. Moreover, we demonstrated that RanBP3’s function during vRNP nuclear export is regulated by phosphorylation at Ser58, and the RanBP3 phosphorylation is modulated by both PI3K/Akt and Ras/ERK/RSK pathways in the late phase of viral infection. In conclusion, this study has shown that RanBP3 is a host factor that has a vital role during the late stage of influenza A virus replication, specifically as a co-factor in CRM1-mediated nuclear export. Identifying this host factor will contribute to the understanding of the mechanism of vRNP transport.

Yes / Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

No description available.

No description available.

No description available.

Thesis (Ph. D.)--University of Virginia, 2007. / Includes bibliographical references. Also available online through Digital Dissertations.

No description available.