On the TRAIL to apoptosis

Baetu, Tudor M.; Hiscott, John

doi:10.1016/s1359-6101(02)00006-0

Cited by 88 publications

(56 citation statements)

References 118 publications

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“…CAML is thought to inhibit the rate of apoptosis in some cells [43]. TNF-related apoptosis-inducing ligand [TRAIL/Apo-2 ligand, tumor necrosis factor, member 10 (TNF SF10)] is a member of the tumor necrosis family that induces apoptosis [44][45][46][47][48][49]. The BCL2 homolog, MCL1, is expressed in human myeloid leukemia cell lines during phorbol ester-induced differentiation along the monocyte/ macrophage pathway.…”

Section: Resultsmentioning

confidence: 99%

Immediate early gene X-1 interacts with proteins that modulate apoptosis

Kumar¹,

Lutz²,

Frank³

et al. 2004

Biochemical and Biophysical Research Communications

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Immediate early gene X-1 (IEX-1) modulates apoptosis, cellular growth, mechanical strain-induced cardiac hypertrophy, and vascular intimal hyperplasia. To determine how IEX-1 alters apoptosis, we performed yeast two-hybrid studies using IEX-1 as the "bait" protein, and examined interactions between IEX-1 and proteins expressed by a human kidney cDNA expression library. We found that IEX-1 interacts with several proteins of which at least four are known to play a role in the regulation of apoptosis: (1) calcium-modulating cyclophilin ligand; (2) tumor necrosis factor-related apoptosisinducing ligand (tumor necrosis factor superfamily, member 10); (3) ML-1 myeloid cell leukemia gene encoded protein; and (4) BAT3, a gene present in the major histo-compatibility complex. Our data suggest that IEX-1 may regulate apoptosis by directly interacting with various proteins involved in the control of apoptotic pathways. KeywordsIEX-1; gly96; 1,25-Dihydroxyvitamin D; ApoptosisThe human immediate early gene X-1 (IEX-1, also known as Dif2, and murine orthologs gly96 and PRG1) plays a role in the control of apoptosis and cellular growth [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The gene (gly96) was initially identified in mouse fibroblasts as a serum-regulated, glycosylated, immediate early gene [1]. The messenger RNA of a similar gene (p22/PRG1) is induced in rat pancreatic cells by pituitary adenylate cyclase activating peptide (PACAP) [20]. The human ortholog of gly96 and PRG1, IEX-1, was identified as an X-radiation induced in fibroblasts by Kondratyev et al. [2], and as a UV-radiation and 1α, 25-dihydroxyvitamin D 3 -regulated gene in human keratinocytes [3,4].Increased expression of IEX-1 is associated with an increase in the growth rate of keratinocytes and HeLa cells, and disruption of IEX-1 gene expression in HeLa cells and 293 cells is associated with a decrease in cellular proliferation [3,7,8,21]. IEX-1 has been shown to be induced in cardiomyocytes and vascular smooth muscle cells by mechanical stretch, and overexpression of IEX-1 in vascular smooth muscle cells protects against stretch-induced hypertrophy [9,15] IEX-1 is regulated by a variety of factors. IEX-1 expression is increased by serum, X-, and UV-irradiation, growth factors such as epidermal growth factor, inflammatory stimuli such as lipopolysaccharide and ceramide, retinoids such as all-trans-retinoic acid or cis-retinoic acid, and by over-expression of Sp1 in cells [1][2][3]6,10,11,20,[24][25][26][27][28][29][30][31]. The gene is repressed by steroid hormones such as 1α, 25-dihydroxyvitamin D 3 and by over-expression of p53 [3,4,30,32]. 1α, 25-Dihydroxyvitamin D 3 also results in a redistribution of IEX-1 from the nucleus into the peri-nuclear and cytoplasmic space. The ratio of Sp1 to p53 within the cell appears to regulate the amount of IEX-1 expression present within the cell [30]. Slight modifications of IEX-1 transcription are observed by mutating putative elements for p300, Sox, NFκB, and AP4 within the prom...

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Section: Resultsmentioning

confidence: 99%

Immediate early gene X-1 interacts with proteins that modulate apoptosis

Kumar¹,

Lutz²,

Frank³

et al. 2004

Biochemical and Biophysical Research Communications

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“…Only two of them, TRAIL R1 (DR4) and TRAIL R2 (DR5), contain functional DDs and can initiate apoptosis upon ligand binding. 20 The others are thought to act as the decoy receptors (DcR) and their expression is thought to provide protection from TRAIL activity in normal cells. TRAIL is believed to be nontoxic to most normal cells in vitro or if delivered systemically in vivo, while at the same time inducing apoptosis in many tumor cell lines.…”

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confidence: 99%

Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Rubinchik

Woraratanadharm

et al. 2003

Cancer Gene Ther

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Brain tumors (BTs) are among the most malignant forms of human cancer. Unfortunately, current treatments are often ineffective and produce severe side effects. Cytotoxic gene therapy is an alternative treatment strategy, with the potential advantages of reduced toxicity to normal brain tissue. Apoptosis-inducing ''death ligands'' Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) are genes with substantial cytotoxic activity in susceptible tumor cells. Here, we compared the effectiveness of Ad vectormediated delivery of Fas ligand-green fluorescent protein (FasL-GFP) fusion protein, human TRAIL, and both genes simultaneously. We examined a panel of 13 cell lines (eight derived from primary isolates) for susceptibility to Ad5-based vector infection and for sensitivity to FasL-and TRAIL-mediated apoptosis. All cell lines were efficiently transduced, but, as expected, varied in their sensitivity to ligand-induced apoptosis. Generally, sensitivity to FasL-GFP correlated with cell surface FasR levels, but no such correlation was seen for TRAIL and its functional receptors, DR4 and DR5. The vector expressing both FasL-GFP and TRAIL was more effective than either of the single-gene vectors at comparable transduction levels, and it was effective against a broader range of cell lines. In five cell lines, coexpression resulted in apoptosis levels greater than those predicted for strictly additive activity of the two death ligands. We believe that Ad vector-mediated delivery of multiple death ligands may be developed as a potential BT therapy, either alone or in conjunction with surgical resection of the primary tumor.

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“…Crosslinking of the two apoptosis-inducing TRAIL receptors (TRAIL-R1 and TRAIL-R2) results in the recruitment of FADD and caspase-8 to the DISC (Srivastava, 2001;Baetu and Hiscott, 2002;Kiechle and Zhang, 2002;Rossi and Gaidano, 2003). The death effector domain of FADD interacts with the death effector domain of procaspase-8 and thereby recruits this proenzyme to the DISC.…”

Section: Ubiquitination Apoptosis and Cancermentioning

confidence: 99%