Activation of the NF-kB pathway mediates apoptotic cell death human stem cells during interspecies competition.

Background—Rel/NF-kB, an oxidative stress–responsive transcription factor, participates transiently in the control of gene expression. The cellular mechanisms that mediate NF-kB activation during ischemia (and during reperfusion in the course of treating ischemia) are not known. Methods and Results—To investigate the NF-kB activation induced during oxidative stress, we examined human cardiac ti...

The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-KB (NF-KB),...

Both STAT3 and NF-kB are persistently activated in diverse cancers and promote tumor cell proliferation, survival, angiogenesis, and metastasis through transcriptional activation of multiple common genes. Paradoxically, STAT3 also suppresses many NF-kB–inducible genes involved in innate and adaptive antitumor immunity in spite of elevated levels of NF-kB in tumors. In this study, we show that e...

Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia (ATL). The viral protein Tax induces the activation and nuclear translocalization of transcription factor NF-kB, which is proposed to play a crucial role in the transformation of T cells by HTLV-I. However, the HTLV-I genes including Tax are not expressed significantly in primary leukemic cells from ATL p...

b1-integrin induction enhances breast cancer cell survival after exposure to ionizing radiation (IR), but the mechanisms of this effect remain unclear. Although NF-kB initiates prosurvival signaling pathways post-IR, the molecular function of NF-kB with other key elements in radioresistance, particularly with respect to extracellular matrix-induced signaling, is not known. We discovered a typic...

b1-integrin induction enhances breast cancer cell survival after exposure to ionizing radiation (IR), but the mechanisms of this effect remain unclear. Although NF-kB initiates prosurvival signaling pathways post-IR, the molecular function of NF-kB with other key elements in radioresistance, particularly with respect to extracellular matrix-induced signaling, is not known. We discovered a typic...

N uclear factor (NF)-kB is a key player in the control of both innate and adaptive immunity. NF-kB proteins are present in the cytoplasm in association with inhibitory proteins called inhibitors of kB (IkBs). On activation by a large plethora of inducers, the IkB proteins are phosphorylated, ubiquitinated, and subsequently degraded in the proteasomes. Degradation of IkBs allows translocation of...

The molecular mechanisms by which multiple myeloma (MM) cells evade glucocorticoid-induced apoptosis have not been delineated. Using a human IgAk MM cell line (ARP-1), we found that dexamethasone (Dex)-induced apoptosis is associated with decreased NF-kB DNA binding and kBdependent transcription. Both nuclear p50:p50 and p50:p65 NF-kB complexes are detected in ARP-1 cells by supershift electrop...