Fas ligand (FasL) is produced by activated T cells and natural killer cells and it induces apoptosis (programmed cell death) in target cells through the death receptor Fas/Apol/CD95. One important role of FasL and Fas is to mediate immune-cytotoxic killing of cells that are potentially harmful to the organism, such as virus-infected or tumour cells. Here we report the discovery of a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds to FasL and inhibits FasL-induced apoptosis. The DcR3 gene was amplified in about half of 35 primary lung and colon tumours studied, and DcR3 messenger RNA was expressed in malignant tissue. Thus, certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL.

Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2^q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain.z 1999 Federation of European Biochemical Societies.

This paper reports that there are major fferences between mammalian cell lines in the propensity to progress into subsequent cell cycles when mitosis is inhibited with agents that disrupt the assembly of the mitotic spindle apparatus (Colcemid, nocodazole, and taxol). Human HeLa S3 cells, which represent one extreme, remain arrested in mitosis, with elevated levels of cyclin B and p34cdc2 kinase activity. InChinese hamster ovary cells, at the other extreme, the periodic rise and fall of cyclin B levels and p34cdc2 kinase activity is only transiently inhibited in the absence of mitosis. The cells progress into subsequent cell cycles, without dividing, resulting in serial doublings of cellular DNA content. In general, the propensity to progress into subsequent cell cycles in the absence of mitosis appears to be species related, such that human cell lines remain permanently blocked in a mitotic state, whereas rodent cell lines are only transiently inhibited when spindle assembly is disrupted. We interpret these results to indicate that in mammalian cell lines there exists a checkpoint which serves to couple cell cycle progression to the completion of certain karyokinetic events. Furthermore, either such a checkpoint exists in some cell lines but not in others or the stringency of the control mechanism varies among different cell lines.Current understanding of the cell cycle is based upon models in which phase transitions are regulated by complex networks of biochemical events, many of which are highly conserved in all eukaryotes. The activation of protein complexes containing the p34cdc2 kinase is central to the transitions from G1 to S and from interphase to mitosis (1-3). The proper temporal order of cell cycle processes is maintained by control mechanisms which ensure that the initiation oflater cell cycle events is dependent on the completion of earlier events (4).The activation of p34cdc2 to initiate the events of mitosis, for example, is modulated by several gene products that serve to couple mitosis to the completion of DNA synthesis and repair, as well as nutrient state and cell size (4, 5). It has been hypothesized that control mechanisms also exist that serve to couple the exit from mitosis with the correct assembly of the spindle apparatus (2).In this paper, we report that major differences exist between mammalian cell lines in the ability to proceed into the next cell cycle when mitosis is inhibited with agents that disrupt microtubule polymerization. These differences are correlated with differences in the modulation of p34cdc2 activity, as well as cellular concentrations of cyclin B, and indicate that mammalian cells differ significantly in the regulation of the transition from mitosis into subsequent cell cycles. MATERIALS AND METHODSCell Culture and Drug Treatment. HeLa S3 and Chinese hamster ovary cells strain AA8 (CHO-AA8) were maintained in minimal essential media a, supplemented with 10% fetal bovine serum, gentamicin at 50 ug/ml, and 2 mM glutamine, buffered with 10 mM Hepes at pH 7.4, ...

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