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Detection of functional single-nucleotide polymorphisms that affect apoptosis

Human EBV-transformed B lymphocyte cell lines (LCLs) were used to measure the apoptotic response of individuals to gamma radiation. The responses form a normal distribution around a median of 35.5% apoptosis with a range of 12-58%. This heterogeneous...
Authors: Harris SL, Gil G, Robins H, Hu W, Hirshfield K, Bond E, Bond G and Levine AJ

WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells

In Wolfram syndrome, a rare form of juvenile diabetes, pancreatic ss-cell death is not accompanied by an autoimmune response. Although it has been reported that mutations in the WFS1 gene are responsible for the development of this syndrome, the...
Authors: Fonseca SG, Fukuma M, Lipson KL, Nguyen LX, Allen JR, Oka Y and Urano F

Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8

Although caspase-2 is believed to be involved in death receptor-mediated apoptosis, the exact function, mode of activation, and regulation of caspase-2 remain unknown. Here we show that protein kinase (PK) CK2 phosphorylates procaspase-2 directly at...
Authors: Shin S, Lee Y, Kim W, Ko H, Choi H and Kim K

Rac1 Leads to Phosphorylation-dependent Increase in Stability of the p66shc Adaptor Protein: Role in Rac1-induced Oxidative Stress

The rac1 GTPase and the p66shc adaptor protein regulate intracellular levels of reactive oxygen species (ROS). We examined the relationship between rac1 and p66shc. Expression of constitutively active rac1 (rac1V12) increased phosphorylation, reduced...
Authors: Khanday FA, Yamamori T, Mattagajasingh I, Zhang Z, Bugayenko A, Naqvi A, Santhanam L, Nabi N, Kasuno...

The Smad6-histone deacetylase 3 complex silences the transcriptional activity of the glucocorticoid receptor: potential clinical implications

Glucocorticoids play pivotal roles in the maintenance of homeostasis but, when dysregulated, may also have deleterious effects. Smad6, one of the transforming growth factor beta (TGFbeta) family downstream transcription factors, interacts with the...
Authors: Ichijo T, Voutetakis A, Cotrim AP, Bhattachryya N, Fujii M, Chrousos GP and Kino T

Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system

The Sleeping Beauty (SB) transposon system is a nonviral DNA delivery system in which a transposase directs integration of an SB transposon into TA-dinucleotide sites in the genome. To determine whether the SB transposon system can mediate stable...
Authors: Huang X, Wilber AC, Bao L, Tuong D, Tolar J, Orchard PJ, Levine BL, June CH, McIvor RS, Blazar BR...

Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways

We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions....
Authors: Richards S, Liu ST, Majumdar A, Liu JL, Nairn RS, Bernier M, Maher V and Seidman MM

Apoptosis Induced by a New Member of Saponin Family Is Mediated through Caspase-8-Dependent Cleavage of Bcl-2

OSW-1 is a new member of cholestane saponin family, which is cytotoxic against many types of malignant cells. The present works showed that OSW-1 induced apoptosis of mammalian cells in a concentration- and time- dependent manner. The drug-induced...
Authors: Zhu J, Xiong L, Yu B and Wu J

Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis

PURPOSE: Raf-1 kinase inhibitor protein (RKIP) was originally identified as the first physiologic inhibitor of the Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathway. This pathway regulates fundamental...
Authors: Hagan S, Al-Mulla F, Mallon E, Oien K, Ferrier R, Gusterson B, Garcia JJ and Kolch W

The inositol phosphatase SHIP-2 down-regulates FcgammaR-mediated phagocytosis in murine macrophages independently of SHIP-1

FcgammaR-mediated phagocytosis of IgG-coated particles is a complex process involving the activation of multiple signaling enzymes and is regulated by the inositol phosphatases PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SHIP-1...
Authors: Ai J, Maturu A, Johnson W, Wang Y, Marsh CB and Tridandapani S