Keap1 moderates the transcription of virus induced genes through G9a-GLP and NFκB p50 recruitment.

Cells must control genes that are induced by virus infection to mitigate deleterious consequences of inflammation. We investigated the mechanisms whereby Keap1 moderates the transcription of genes that are induced by Sendai virus infection in mouse embryo fibroblasts (MEFs). Keap1-/- deletions increased the transcription of virus induced genes independently of Nrf2.

Virus Infection Induces Keap1 Binding to Cytokine Genes, Which Recruits NF-κB p50 and G9a-GLP and Represses Cytokine Transcription.

Proinflammatory cytokine gene transcription must be moderated to avoid the pathological consequences of excess cytokine production. The relationships between virus infection and the mechanisms that moderate cytokine transcription are incompletely understood. We investigated the influence of Keap1 on cytokine gene induction by Sendai virus infection in mouse embryo fibroblasts.

ATR-101 inhibits cholesterol efflux and cortisol secretion by ATP-binding cassette transporters, causing cytotoxic cholesterol accumulation in adrenocortical carcinoma cells.

Background And Purpose: To further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR-101 (PD132301-02).

Experimental Approach: We compared the effects of ATR-101, PD129337, and ABC transporter inhibitors on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC-derived cell lines. We examined the effects of these compounds in combination with methyl-β-cyclodextrin or exogenous cholesterol to determine the roles of altered cholesterol levels in the effects of these compounds.

Visualization of the Genomic Loci That Are Bound by Specific Multiprotein Complexes by Bimolecular Fluorescence Complementation Analysis on Drosophila Polytene Chromosomes.

We have developed a procedure that enables visualization of the genomic loci that are bound by complexes formed by a specific combination of chromatin-binding proteins. This procedure is based on imaging bimolecular fluorescence complementation (BiFC) complexes on Drosophila polytene chromosomes. BiFC complexes are formed by the facilitated association of two fluorescent protein fragments that are fused to proteins that interact with, or are in close proximity to, each other.