Key to the pathogenicity of several viruses is activation of the canonical nuclear factor-kappaB (NF-kappaB) transcriptional pathway. Subversion of this tightly regulated mechanism is achieved through the production of host mimetic viral proteins that deregulate the transcription process. One such protein is ks-vFLIP (produced by the Kaposi's sarcoma herpes virus [KSHV]), which associates with IKKgamma, an essential component of the IKK complex or signalosome. This interaction renders the canonical NF-kappaB pathway constitutively active and has been linked to Kaposi's sarcoma and other malignancies. In order to elucidate the molecular basis underpinning ks-vFLIP-induced activation of the IKK signalosome, we have determined the crystal structure of a complex involving a fragment of IKKgamma bound to ks-vFLIP at 3.2 A. In addition to identifying and subsequently probing the ks-vFLIP-IKKgamma interface, we have also investigated the effects of a mutation implicated in the genetic disorder anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID).
vectors (LVs) that are targeted to APC using a chimeric measles virus (MV) hemagglutinin (H). The MV H protein is mutated to prevent binding to MV receptors and incorporates a single-chain antibody that recognizes murine major histocompatibility complex class II (MHC II). This targeted LV is highly efficient in transduction of freshly isolated mouse B cells and dendritic cells. MHC II-positive cells in spleen are transduced after intravenous injection, and a robust immune response to an antigen transgene is generated.
Background: Regulation and function of the apoptotic nuclease, caspase-activated DNase (CAD), remains obscure.Results: Rapid depletion of the CAD inhibitor (ICAD) using auxin-inducible degron system induces ectopic CAD activation and apoptosis.Conclusion: Ectopic CAD activation triggers caspase activation and apoptosis through a positive feedback loop.Significance: Controlled CAD dissociation from ICAD is applicable as a novel method to eliminate unwanted cells.
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