The NF-kB pathway is a ubiquitous stress response that activates the NF-kB family of transcription factors. Antigen receptors, receptors of the innate immune system, and certain intracellular stressors are potent activators of this pathway. The transcriptional program that is activated is both antiapoptotic and highly proinflammatory. Indeed, any compromise in engagement of the pathway results ...

Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington’s disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several bio...

BACKGROUND Tick Subolesin and its ortholog in insects and vertebrates, Akirin, have been suggested to play a role in the immune response through regulation of nuclear factor-kappa B (NF-kB)-dependent and independent gene expression via interaction with intermediate proteins that interact with NF-kB and other regulatory proteins, bind DNA or remodel chromatin to regulate gene expression. The obj...

We have cloned the cDNA encoding IKB-I~, one of the two major IKB isoforms in mammalian cells. The recombinant IKB-p protein interacts with equal affinity to p65 and c-Rel and does not exhibit a preference between these Rel proteins, instead the primary difference between IKB-a and IKB-I~ iS in their response to different inducers of NF-KB activity. One class of inducers causes rapid but transi...

Chronic active Epstein-Barr virus infection (CAEBV) represents a new subtype of lymphoproliferative disorders characterized by high morbidity and mortality rates and often leads to malignant transformation of infected cells. Efficient therapeutic strategies are presently unavailable; therefore, the development of therapies to prevent CAEBV-mediated transformation and disease progression is cruc...

Syndromes of type 2 diabetes and insulin resistance are accompanied by varying degrees of hyperinsulinemia. To date, a number of epidemiological studies have suggested that elevated levels of circulating insulin contribute independently to cardiovascular risk.1,2 It is not surprising, however, that some studies demonstrated no, or marginally increased, risk for cardiovascular complications,3,4 ...

Inflammatory responses in eucaryotic cells are often associated with oscillations in the nuclear-cytoplasmic translocation of the transcription factor NF-kB. In most laboratory realizations, the oscillations are triggered by a cytokine stimulus. We use a mathematical model to show that an oscillatory external stimulus can synchronize the NF-kB oscillations into states where the ratios of the in...

EGF activates NF-kB, and constitutively activated NF-kB contributes to EGFR mutation-associated tumorigenesis, but it remains unclear precisely how EGFR signaling leads to NF-kB activation. Here we report that CARMA3, a caspase recruitment domain (CARD)-containing scaffold molecule, is required for EGF-induced NFkB activation. CARMA3 deficiency impaired the activation of the IKK complex followi...

We determined whether blockade of nuclear factor (NF)-kB/relA activity in human ovarian cancer cells can suppress angiogenesis and growth in an orthotopic nude mouse model. The human ovarian cancer cells SKOV3ip.1 and HEY-A8 were transfected with a mutated IkBa (IkBaM), i.e., resistant to phosphorylation and degradation, and hence blocks NF-kB activity. NF-kB signaling blockade significantly in...

Purpose:Near equal rates of incidence and mortality emphasize the need for novel targeted approaches for better management of patients with pancreatic cancer. Inflammatory molecules NF-kB and STAT3 are overexpressed in pancreatic tumors. Inhibition of one protein allows cancer cells to survive using the other. The goal of this study is to determine whether targeting STAT3/NF-kB crosstalk with a...