The death effector domain protein family: regulators of cellular homeostasis

Tibbetts, Michael D.; Zheng, Lixin

doi:10.1038/ni0503-404

Cited by 201 publications

(159 citation statements)

References 74 publications

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“…The DISC appears to contain a specific stoichiometric ratio of proteins (3 : 3 : 3), which are organized by the trimeric structure of the preassembled Fas receptor (Siegel et al, 2000). In fact, mutant (defective) Fas cannot recruit three FADD molecules and consequently do not form a DISC (review in Tibbetts et al, 2003). In rat brain tissue, only the monomeric form of procaspase-8 was immunodetected as described in other cell systems (see Donepudi et al, 2003).…”

Section: Regulation Of Fadd By Opiate Drugsmentioning

confidence: 99%

“…Besides the role of Fas/FADD in apoptosis, there are now solid evidences that also demonstrate the relevance of this system in the regulation of cell growth and differentiation (Budd, 2002;Tibbetts et al, 2003) and in regenerative responses in neurons Lambert et al, 2003). These nonapoptotic roles for Fas/FADD are still poorly understood and may involve the activation of the ERK1/2 MAPK pathway, which is important for antiapoptotic signals (Holmström et al, 1999(Holmström et al, , 2000Wada and Penninger, 2004) and for the regulation of synaptic plasticity, learning, and memory (Kyosseva, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

García-Fuster

Miralles

Garcı́a-Sevilla

2006

Neuropsychopharmacol

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This study was designed to assess the effects of opiate treatment on the expression of Fas-associated protein with death domain (FADD) in the rat brain. FADD is involved in the transmission of Fas-death signals that have been suggested to contribute to the development of opiate tolerance and addiction. Acute treatments with high doses of sufentanil and morphine (m-agonists), , and U50488H (k-agonist) induced significant decreases (30-60%) in FADD immunodensity in the cerebral cortex, through specific opioid receptor mechanisms (effects antagonized by naloxone, naltrindole, or nor-binaltorphimine). The cannabinoid CB 1 receptor agonist WIN 55,212-2 did not alter FADD content in the brain. Chronic (5 days) morphine (10-100 mg/kg), SNC-80 (10 mg/kg), or U50488H (10 mg/kg) was associated with the induction of tachyphylaxis to the acute effects. In morphine-and SNC-80-tolerant rats, antagonistprecipitated (2 h) or spontaneous withdrawal (24-48 h) induced a new and sustained inhibition of FADD (13-50%). None of these treatments altered the densities of caspases 8/3 (including the active cleaved forms) in the brain. Pretreatment of rats with SL 327 (a selective MEK1/2 inhibitor that blocks ERK activation) fully prevented the reduction of FADD content induced by SNC-80 in the cerebral cortex (43%) and corpus striatum (29%), demonstrating the direct involvement of ERK1/2 signaling in the regulation of FADD by the opiate agonist. The results indicate that m-and d-opioid receptors have a prominent role in the modulation of FADD (opposite to that of Fas) shortly after initiating treatment. Opiate drugs (and specifically the d-agonists) could promote survival signals in the brain through inhibition of FADD, which in turn is dependent on the activation of the antiapoptotic ERK1/2 signaling pathway.

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Section: Regulation Of Fadd By Opiate Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

García-Fuster

Miralles

Garcı́a-Sevilla

2006

Neuropsychopharmacol

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“…Importantly, both effects are achieved through suppression of mitotic Cdk1, although further studies are required to fully understand the mechanism of how DEDD suppresses mitotic Cdk1 activity. Nonetheless, such new insights may further implicate the mitotic phase during the cell cycle as a crucial period involved in balancing mammalian cell size.Although the DED-containing molecules were initially supposed to be involved in apoptosis regulation, evidence has accumulated that they have diverse functions (35,36). For instance, Arechiga et al (37) reported that FADD and caspase-8, also DED-containing family members, play essential roles in maintaining S6K1 activity during G 1 /S phases by modulating Cdk2 in T cells.…”

mentioning

confidence: 99%

The Death Effector Domain-containing DEDD Supports S6K1 Activity via Preventing Cdk1-dependent Inhibitory Phosphorylation

Kurabe

Arai

Nishijima

et al. 2009

Journal of Biological Chemistry

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؊/؊ cells and tissues. Consequently, as in S6K1 ؊/؊ mice, the insulin mass within pancreatic islets was reduced in DEDD ؊/؊ mice, resulting in glucose intolerance. These findings suggest a novel cell sizing mechanism achieved by DEDD through the maintenance of S6K1 activity prior to cell division. Our results also suggest that DEDD may harbor important roles in glucose homeostasis and that its deficiency might be involved in the pathogenesis of type 2 diabetes mellitus.Cell size is closely related to specialized cell function and to the specific patterning of tissues in the body. Cell sizing is regulated mainly by two mechanisms: cell cycle control and the biochemical response to nutrients and/or growth factors (1-5). During cell cycle progression, both the G 1 (which is believed to be dominant) and the G 2 periods are important for cells to increase their volume (6 -9). In addition, we recently provided evidence that the mitotic period (M phase) also influences cell size, through analysis of DEDD-deficient mice (10, 11). The DEDD molecule was initially described as a member of the death effector domain (DED) 2 -containing protein family (12). Although the absence of DEDD did not apparently influence progression of apoptosis (10), we found that during mitosis, DEDD is associated with Cdk1-cyclin B1 and that it decreases the kinase activity of Cdk1. This response impedes the Cdk1-dependent mitotic program to shut off synthesis of ribosomal RNA (rRNA) and protein and is consequently useful in gaining sufficient cell growth prior to cell division. Depletion of DEDD consistently results in a shortened mitotic duration and an overall reduction in the amount of cellular rRNA and protein and, furthermore, in cell and body size (10,11).Of the biochemical responses responsible for cell sizing, the signaling cascade involving phosphatydilinositol 3-kinase (PI3K) and its downstream target of rapamycin (TOR) is most crucial (13)(14)(15). In mammals, upon stimulation by growth factors, including insulin, the mammalian TOR (mTOR) cooperates with PI3K-dependent effectors to activate S6K1, thereby phosphorylating the 40 S ribosomal protein S6, and subsequently enhances translation of the 5Ј-terminal oligopyrimidine sequences that encode components of the translational machinery. This reaction increases the number of ribosomes and the efficacy of protein synthesis, thus critically promoting cell growth (16 -18). Therefore, mice deficient for S6K1 (S6K1 Ϫ/Ϫ ) had reduced cell and body size (19 -23). This effect also involves S6K1 in maintenance of glucose tolerance. S6K1 * This work was supported, in whole or in part, by National Institutes of Health Grant 5RO1AI50948-05. This work was also supported by grants-in-aid from the Ministry of Education, Sports, Culture, Science, and Technology, Japan, the Takeda Science Foundation (to T. M. and S. A.), the Mitsubishi Pharma Research Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Danone Institute of Nutrition for Health, the Uehara Memorial Fou...

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“…29 Mn 2 þ -mediated caspase-8 activation was independent of the classical FADD pathway in our model since overexpression of a dominant-negative form of FADD lacking the DED domain that abolished the TRAIL response 24 (Figure 5) did not prevent caspase-8 activation and apoptosis triggered by Mn 2 þ . Similar FADD-independent caspase-8 activation has already been described in other models using other apoptotic stimuli.…”

Section: Discussionmentioning

confidence: 70%

p38 MAPK and MSK1 mediate caspase-8 activation in manganese-induced mitochondria-dependent cell death

et al. 2007

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Heavy metals are important regulators of cell apoptosis. Manganese (Mn 2 þ ) is a potent inducer of apoptosis in different cell types, but the precise mechanisms that mediate such effects are not well defined. We previously reported that Mn 2 þ was a potent apoptotic agent in human B cells, including lymphoma B cell lines. We show here that Mn 2 þ -induced cell death in human B cells is associated with caspase-8-dependent mitochondrial activation leading to caspase-3 activity and apoptosis. We used specific caspase-8 interfering shRNAs to reduce caspase-8 expression, and this also reduced Mn 2 þ -induced caspase-3 activation and apoptosis. Mn 2 þ -triggered caspase-8 activation is associated with a specific pathway, which is independent of Fas-associated death domain protein, and dependent on the sequential activation of p38-mitogen-activated protein kinase (p38 MAPK) and mitogen-and stress-response kinase 1 (MSK1). Inhibition of p38 activity using either pharmacological inhibitors or dominant-negative mutant forms of p38 blocked Mn 2 þ -mediated phosphorylation of MSK1 and blocked subsequent caspase-8 activation. However, specific inhibitors and the expression of a dominant-interfering mutant of MSK1 only inhibited caspase-8 activation, but not p38 activity. These findings suggest a novel model for the regulation of caspase-8 during Mn 2 þ -induced apoptosis based on the sequential activation of p38 MAPK, MSK1, caspase-8 and mitochondria, respectively.

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The death effector domain protein family: regulators of cellular homeostasis

Cited by 201 publications

References 74 publications

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

The Death Effector Domain-containing DEDD Supports S6K1 Activity via Preventing Cdk1-dependent Inhibitory Phosphorylation

p38 MAPK and MSK1 mediate caspase-8 activation in manganese-induced mitochondria-dependent cell death

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