Atherosclerosis is an inflammatory disease, characterized by the accumulation of macrophage-derived foam cells in the vessel wall and accompanied by the production of a wide range of chemokines, cytokines, and growth factors. These factors regulate the turnover and differentiation of immigrating and resident cells, eventually influencing plaque development. One of the key regulators of inflamma...

Glucocorticoids exert their effects on gene transcription through ubiquitous receptors that bind to regulatory sequences present in many genes. These glucocorticoid receptors are present in all cell types, yet glucocorticoid action is controlled in a tissue-specific way. One mechanism for this control relies on tissue-specific transcriptional activators that bind in the vicinity of the glucocor...

The transcription factor nuclear factor erythroid-2 is over-expressed in patients with myeloproliferative neoplasms irrespective of the presence of the JAK2(V617F) mutation. Our transgenic mouse model over-expressing nuclear factor erythroid-2, which recapitulates many features of myeloproliferative neoplasms including transformation to acute myeloid leukemia, clearly implicates this transcript...

In an effort to determine the localization of fibroblast growth factor (FGF) receptors (FGFR) that could mediate the intracellular action of FGF-2, we discovered the presence of high-affinity FGF-2 binding sites in the nuclei of bovine adrenal medullary cells (BAMC). Western blot analysis demonstrated the presence of 103-, 118-, and 145-kDa forms of FGFR1 in nuclei isolated from BAMC. 125I-FGF-...

Ligand-receptor internalization has been traditionally regarded as part of the cellular desensitization system. Low-density lipoprotein receptor-related protein (LRP) is a large endocytosis receptor with a diverse array of ligands. We recently showed that LRP binds heparin-binding growth factor midkine. Here we demonstrate that LRP mediates nuclear targeting by midkine and that the nuclear targ...

The mitochondrial deacetylase SIRT3 regulates several important metabolic processes. SIRT3 is transcriptionally upregulated in multiple tissues during nutrient stresses such as dietary restriction and fasting, but the molecular mechanism of this induction is unclear. We conducted a bioinformatic study to identify transcription factor(s) involved in SIRT3 induction. Our analysis identified an en...

The notion that nuclear factor-KB (NF-KB) is a tumorpromoting transcription factor has become a widely accepted dogma in biology. However, recent findings suggest an inhibitory role for NF-KB in carcinogenesis and tumorigenesis. Although the tumor suppressor–like effect of NF-KB remains to be rigorously established by further studies using cellular and animal models, these latest findings warra...

To the Editor:—In their very interesting study, Loop et al. demonstrate an inhibitory effect of thiopental on nuclear factor B (NFB) activation in T cells. However, we missed some essential background information in the discussion. First, the concentration of thiopental used in this study is much higher than plasma concentrations noted in clinical practice or in other models presenting inhibito...

Nuclear factor (NF)-κB transcription factors are pivotal regulators of innate and adaptive immune responses, and perturbations of NF-κB signaling contribute to the pathogenesis of immunological disorders. NF-κB is a well-known proinflammatory mediator, and its deregulated activation is associated with the chronic inflammation of autoimmune diseases. Paradoxically, NF-κB plays a crucial role in ...

Acknowledgements We apologize to the many researchers whose work we have not been able to discuss in this limited review. A. H. thanks X.-F. Qin and T. H. Leung for longstanding collaboration and communication of unpublished results, G. Ghosh for figures of protein structures, and E. A. Komives, G. Ghosh, and V. Sivakumar for insightful discussions. Summary: Over the past few years, the transcr...