Hatano, Etsuro, and David A. Brenner Akt protects mouse hepatocytes from TNF-aand Fas-mediated apoptosis through NK-kB activation. Am J Physiol Gastrointest Liver Physiol 282: G1357–G1368, 2002.—To determine the role of phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor-kB (NF-kB) in protecting hepatocytes from tumor necrosis factor-a (TNF-a)and Fas-mediated apoptosis, we pretreated pr...

Melanoma tumors and cultured cell lines are relatively resistant to the cytotoxic effects of ionizing radiation, thereby limiting the use of radiotherapy for the clinical treatment of melanoma. New strategies for sensitizing melanoma cells therefore deserve examination. In an attempt to identify and target signaling pathways that contribute to radioresistance, we investigated the role of nuclea...

The response of mammalian cells to stress is controlled by transcriptional regulatory proteins such as nuclear factor KB iNT-Kit i to induce a wide variety of early response genes. In this report, we show that exposure of cells to hypoxia (0.02% (>,) results in IK-HI» degradation, increased N1 -H-IÕ DNA binding activity, and transactivation of a reporter gene con struct containing two NF-KB D...

Stratified epithelium contains a mitotically active basal layer of cells that cease proliferating, then migrate outwards and undergo terminal differentiation. The control of this process, which is abnormal in cutaneous neoplasia and inflammation, is not well understood. In normal epidermis, NF-kB proteins were found to exist in the cytoplasm of basal cells and then to localize in the nuclei of ...

Nuclear transcription factor NF-kB, initially discovered as a factor in the nucleus of B cells that binds to the enhancer of the kappa light chain of immunoglobulin, has since been shown to be expressed ubiquitously in the cytoplasm of all cell types, conserved from Drosophila to man. It translocates to the nucleus only when activated, where it regulates the expression of over 200 genes that co...

(Baeuerle and Baltimore, 1996). More than a decade ago, the transcriptional activator In vivo, phosphorylation of IkB occurs when it is comNF-kB was described as a protein that bound to a speplexed with NF-kB and does not cause dissociation of cific DNA site in the intronic enhancer of the immunothe complex. Rather, it signals ubiquitination of IkB, globulin k light chain gene (Sen and Baltimor...

Purpose: Although the KRAS mutation is one of critical genetic alterations in endometrial carcinogenesis, the downstream targets are not known. Experimental Design: In this study, we investigated the molecular targets of KRAS signals, using tumorigenic cells with oncogenic KRASmutation established from telomerase reverse transcriptase (TERT)immortalized endometrial epithelial cells. Results: We...

Purpose: NF-kB is a transcription factor known to promote tumorigenesis. However, NF-kB is also known to be proapoptotic andmay potentially function as a tumor suppressor, although such a functional role has not been extensively investigated in human cancer. Experimental Design: A dominant-negative mutant of IkBawithmutations at S32A and S36Awas used to inhibit the function of NF-kB in ovarian ...

The NF-kB pathway plays an important role in regulating the immunity response in animals. In this study, small interfering RNAs (siRNA) were used to specifically inhibit NF-kB 1 expression and to elucidate the role of NF-kB in the signal transduction pathway of the Salmonella challenge in the chicken HD11 cell line. The cells were transfected with either NF-kB 1 siRNA, glyceraldehyde 3-phosphat...

Activation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kB, AP-1, NFAT, and STAT from the cytoplasm into the nucleus. The first step in the nuclear import process is recognition of a nuclear localization sequence (NLS) within the karyophilic protein by a cytoplasmic receptor such as the importin (karyopherin)-a subunit. The NLSs of NF-kB, AP-1, a...