Mediator is a transcriptional co-activator recruited to enhancers by DNA-binding activators, and it also interacts with RNA polymerase (Pol) II as part of the preinitiation complex (PIC). We demonstrate that a single Mediator complex associates with the enhancer and core promoter in vivo, indicating that it can physically bridge these transcriptional elements. However, the Mediator kinase modul...

The research described in this Thesis is part of a project to develop a new database system for proteo-chemometric research. This new system uses a mediator/wrapper approach for integrating heterogeneous and autonomous data sources. Special-purpose modules for data representation and data analysis can be incorporated into the system through the extensibility of the object-relational mediator. L...

We have demonstrated that caspase-1 is a mediator of both cisplatin-induced acute kidney injury (AKI) and ischemic AKI. As caspase-1 is activated in the inflammasome, we investigated the inflammasome in cisplatin-induced and ischemic AKI. Mice were injected with cisplatin or subjected to bilateral renal pedicle clamping. Immunoblot analysis of whole kidney after cisplatin-induced AKI revealed: ...

Abstract Post-transcriptional gene silencing mediated by microRNAs (miRNAs) modulates numerous developmental and stress response pathways. For the last two decades, HASTY (HST), ortholog of human EXPORTIN 5, was considered to be a candidate protein that exports plant miRNAs from nucleus cytoplasm. Here, we report HST functions in miRNA pathway independent its cargo-exporting activity Arabidopsi...

Clostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1-250 aa, N-domain), which is the catalytic site, and a C-terminal domain (251-370 aa, C-domain), w...

Human Mediator complexes have been described as important bridging factors that enhance the effect of activators in purified systems and in chromatin. Here we report a novel basal function of a human Mediator complex. A monoclonal antibody was generated that depleted the majority of Mediator components from crude cell extracts. The removal of human Mediator abolished transcription by RNA polyme...

The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements...