Hematopoietic progenitor cells (HPC) from mice nullizygous at the Fanconi anemia (FA) group C locus (FAC -/-) are hypersensitive to the mitotic inhibitory effects of interferon (IFN-gamma). We tested the hypothesis that HPC from the bone marrow of Fanconi group C children are similarly hypersensitive and that the fas pathway is involved in affecting programmed cell death in response to low dose...

Apoptosis is initiated via the mitochondrial or the death receptor pathway. Central to the mitochondrial pathway is the release of cytochrome c from the mitochondria, leading to activation of the caspase cascade and execution of apoptosis.1 The mitochondrial pathway is regulated by the BCL-2 family of proteins, i.e. proapoptotic BAX and BAK as well as antiapoptotic BCL-2 and BCL-xL. The death r...

Active Src localization at focal adhesions (FAs) is essential for cell migration. How this pool is linked mechanistically to the large pool of Src at late endosomes (LEs)/lysosomes (LY) is not well understood. Here, we used inducible Tsg101 gene deletion, TSG101 knockdown, and dominant-negative VPS4 expression to demonstrate that the localization of activated cellular Src and viral Src at FAs r...

BACKGROUND/AIMS The hepatitis B virus X protein (HBx) contributes to HBV-induced injury of renal tubular cells and induces apoptosis via Fas/FasL up-regulation. However, the mechanism of Fas/FasL activation is unknown. Recent studies indicated that HBx induction of apoptosis in hepatic cells depends on activating the MLK3-MKK7-JNKs signaling module, which then up-regulates FasL expression. In t...

Autoimmune lymphoproliferative disorders, including autoimmune lymphoproliferative syndrome (ALPS) and Dianzani autoimmune lymphoproliferative disease (DALD), are inherited defects of the Fas apoptotic pathway characterized by lymphoid accumulation and autoimmune manifestations. We report the molecular, clinical, immunologic features and the long-term progress of 31 patients. Four carried Fas g...

BACKGROUND The Fas pathway is a major regulator of T cell homeostasis, however, the T cell population that is controlled by the Fas pathway in vivo is poorly defined. Although CD4 and CD8 single positive (SP) T cells are the two major T cell subsets in the periphery of wild type mice, the repertoire of mice bearing loss-of-function mutation in either Fas (lpr mice) or Fas ligand (gld mice) is p...

Fas triggering by agonistic antibodies or by its cognate ligand, FasL, induces apoptotic cell death, whereas mutation in the Fas death domain is associated with lymphoma progression. On prolonged culture in the presence of an agonistic anti-Fas antibody, we raised a Jurkat cell line resistant to agonistic antibodies but still sensitive to soluble FasL, which carried at the heterozygous state, a...

Cytotoxic T (Tc) cells deficient in perforin lyse Fas-negative targets after lengthy incubation periods. This process is independent of granzymes, and killing occurs via the Fas pathway for the following reasons. Interaction of perforin-deficient Tc cells with Fas-negative targets leads to an up-regulation of Fas that is dependent on Ag recognition, de novo synthesis, and transport of proteins ...

Abreu-Martin, Maria T., Andrew A. Palladino, Mary Faris, Nelson M. Carramanzana, André E. Nel, and Stephan R. Targan. Fas activates the JNK pathway in human colonic epithelial cells: lack of a direct role in apoptosis. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G599–G605, 1999.—Fas is expressed constitutively by colonic epithelial cells, and its ligand is expressed by intraepithelia...

Spontaneous apoptosis was observed in a proportion of peripheral blood mononuclear cells obtained from patients with head and neck cancer (HNC) but not from normal healthy donors (T. Saito et al., Clin. Cancer Res., 5: 1263-1273, 1999). To further investigate this phenomenon, peripheral blood mononuclear cells were obtained from patients with HNC or normal controls (NCs) and evaluated for expre...