potent induction of fetal hemoglobin (hbf) production results in alleviating the complications of β-thalassemia and sickle cell disease (scd). hbf inducer agents can trigger several molecular signaling pathways critical for erythropoiesis. janus kinase/signal transducer and activator of transcription (jak/stat), mitogen activated protein kinas (mapk) and phosphoinositide 3-kinase (pi3k) are con...

The c-Jun N-terminal protein kinase (JNK)/c-Jun and p53 pathways form distinct death-signaling modules in neurons that culminate in Bax-dependent apoptosis. To investigate whether this signaling autonomy is due to recruitment of particular BH3-only proteins, we searched for a toxic signal that would activate both pathways in the same set of neurons. We show that arsenite activates both the JNK/...

cyclooxygenase-2 (cox-2) has a pivotal role in the pathogenesis of the lung cancer. it is known that cox-2 negatively regulates the activity of a number of tumor suppressors, including p53. consequently, inhibition of cox-2 signaling is anticipated to be a promising approach to stabilize p53 functionality. in this regard, we investigated the effect of cox-2 signaling blockade on p53 and cox-2 e...

Cyclooxygenase-2 (COX-2) has a pivotal role in the pathogenesis of the lung cancer. It is known that COX-2 negatively regulates the activity of a number of tumor suppressors, including p53. Consequently, inhibition of COX-2 signaling is anticipated to be a promising approach to stabilize p53 functionality. In this regard, we investigated the effect of COX-2 signaling blockade on p53 and COX-2 e...

The p53 tumor suppressor regulates transcription of genes associated with diverse cellular functions including apoptosis, growth arrest, DNA repair and differentiation. Recently, we established that p53 can modulate expression of Toll-like receptor (TLR) innate immunity genes but the degree of cross-talk between p53 and TLR pathways remained unclear. Here, using gene expression profiling we cha...

Sporadic human tumors and the hereditary cancer predisposition syndrome Li-Fraumeni are frequently associated with mutations in the p53 tumor suppressor gene that compromise its ability to function as a DNA damage checkpoint. A subset of Li-Fraumeni patients with wild-type p53 alleles have mutations in chk2/hcds1, one of the genes signaling the presence of DNA damage to the p53 protein. This su...

Among different pathological conditions that affect human beings, cancer has received a great deal of attention primarily because it leads to significant morbidity and mortality. This is essentially due to increasing world-wide incidence of this disease and the inability to discover the cause and molecular mechanisms by which normal human cells acquire the characteristics that define cancer cel...

Clinical, epidemiological, and experimental evidence indicate that the insulin-like growth factors (IGFs) are important mediators in the biochemical chain of events that lead from a phenotypically normal to a neoplastic cell. The IGF1 receptor (IGF1R), which mediates the biological actions of IGF1 and IGF2, exhibits potent pro-survival and antiapoptotic activities. The IGF1R is highly expressed...

signaling in pluripotent stem cells is a complex and dynamic process involving multiple mediators, finely tuned to balancing pluripotency and differentiation states. characterizing and modifying the necessary signaling pathways to attain desired cell types is required for stem-cell applications in various fields of regenerative medicine. these signals may help enhance the differentiation potent...