The Baculovirus p35 Protein Inhibits Fas- and Tumor Necrosis Factor-induced Apoptosis

Beidler, David; Tewari, Muneesh; Friesen, Paul D.; Poirier, Guy G.; Dixit, Vishva M.

doi:10.1074/jbc.270.28.16526

Cited by 302 publications

(104 citation statements)

References 20 publications

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“…However, this caspase inhibition only partially improved thymocyte survival. Consistent with previous studies in cell lines (42,43), p35 efficiently suppressed anti-Fas-induced cell death, in which caspase-8 is known to play a primary, death-initiating role (reviewed in Ref. 44).…”

Section: Discussionsupporting

confidence: 78%

Caspase Enzyme Activity Is Not Essential for Apoptosis During Thymocyte Development

Doerfler

Forbush

Perlmutter

2000

The Journal of Immunology

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Caspases, a family of cysteine proteases, are critical mediators of apoptosis. To address the importance of caspases in thymocyte development, we have generated transgenic mice that express the baculovirus protein p35, a viral caspase inhibitor, specifically in the thymus. p35 expression inhibited Fas (CD95)-, CD3-, or peptide-induced caspase activity in vitro and conferred resistance to Fas-induced apoptosis. However, p35 did not block specific peptide-induced negative selection in OT1 and HY TCR transgenic mouse models. Even the potent pharmacological caspase inhibitor zVAD-FMK (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone) could not prevent peptide-induced deletion of OT1 thymocytes, although it improved basal thymocyte survival in vitro. Moreover, the developmental block observed in rag1−/− thymocytes, which lack pre-TCR signaling, was also not rescued by p35 expression. These results indicate that caspase-independent signal transduction pathways can mediate thymocyte death during normal T cell development.

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Section: Discussionsupporting

confidence: 78%

Caspase Enzyme Activity Is Not Essential for Apoptosis During Thymocyte Development

Doerfler

Forbush

Perlmutter

2000

The Journal of Immunology

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“…The baculovirus Autographa californica p35 gene product inhibits apoptosis in insects, mammals and nematodes, suggesting that it acts at a central and evolutionarily conserved part of the apoptotic pathway [24,138,146,147]. Purified recombinant p35 inhibits the activity of purified recombinant caspases, including caspases-1, -2, -3 and -4, and maximum inhibition is achieved at equimolar concentrations of p35 and the caspase.…”

Section: P35mentioning

confidence: 99%

Caspases: the executioners of apoptosis

Cohen

1997

Biochemical Journal

4,274

2,938

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Apoptosis is a major form of cell death, characterized initially by a series of stereotypic morphological changes. In the nematode Caenorhabditis elegans, the gene ced-3 encodes a protein required for developmental cell death. Since the recognition that CED-3 has sequence identity with the mammalian cysteine protease interleukin-1β-converting enzyme (ICE), a family of at least 10 related cysteine proteases has been identified. These proteins are characterized by almost absolute specificity for aspartic acid in the P " position. All the caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) pentapeptide activesite motif. Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. Activation of caspases during apoptosis results in the cleavage of critical cellular substrates, including poly(ADP-ribose) poly-

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“…Baculovirus-derived p35 directly binds with activated caspases and inhibits apoptosis [36,37]. Thus, it can prevent apoptosis induced by the TNF/TNFR and FasL/ Fas systems [38].…”

Section: Apoptosis Inductivitymentioning

confidence: 99%

Molecular Characteristics of Porcine Fas-associated Death Domain (FADD) and Procaspase-8

Inoue

Matsuda‐Minehata

Goto

et al. 2007

Journal of Reproduction and Development

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Abstract. To reveal the intracellular signal transduction molecules involved in granulosa cell apoptosis in porcine ovarian follicles, we cloned the porcine Fas-associated death domain (FADD), an adaptor protein for the cell death receptor, and procaspase-8, an initiator caspase. Porcine FADD (pFADD) was 636 bp (211 amino acids: aa) long and showed 74.0 and 65.4% homology with human and murine FADD, respectively. Porcine procaspase-8 (pprocaspase-8) was 1,431 bp (476 aa) long and 70.6 and 63.4% homologous with human and murine procaspase-8, respectively. To confirm the apoptosis-inducing abilities, we constructed pFADD and pprocaspase-8 cDNA expression vectors with enhanced green fluorescence protein (EGFP) and then transfected them into human uterine cervix tumor (HeLa-K), human granulosa cell-derived (KGN), murine granulosa-derived tumor (KK1), and porcine granulosa cell-derived (JC410) cells. When pFADD and pprocaspase-8 were overexpressed, cell death was induced in these transfected cells. However when caspase-inhibitor p35 was cotransfected, cell death was inhibited. The pFADD and pprocaspase-8 genes are well conserved, as are the physiological functions of their products. Key words: Apoptosis, Caspase-8, Fas-associated death domain (FADD), Granulosa cell, Porcine ovary (J. Reprod. Dev. 53: [427][428][429][430][431][432][433][434][435][436] 2007) poptosis is an important phenomenon involved i n c e l l s u r v i v a l a n d / o r d e a t h d u r i n g differentiation and development [1,2]. The death ligand and receptor systems are considered to be apoptosis-inducing factors [3][4][5][6][7]. Death receptors, which belong to the tumor necrosis factor (TNF) receptor family, are membrane-binding proteins with a death domain (DD) in their intracellular regions. An adaptor protein, such as Fasassociating death domain protein (FADD), which has a DD in the C-terminal region and a death effector domain (DED) in the N-terminal region, is recruited when each specific ligand binds to its r e c e p t o r [ 8 -1 0 ] . T h e n , F A D D b i n d s w i t h procaspase-8 (also called FLICE), which has two DEDs in the N-teminal region [11,12]. These molecules compose the death-inducing signaling complex (DISC). As a result of the proteolytic autoactivation of procaspase-8 [13], subunit protein 18 (p18) and 11 (p11) are released into the cytoplasm and reform a proteolytic component that c l e a v e s m a n y s u b s t r a t e p r o t e i n s , s u c h a s

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The Baculovirus p35 Protein Inhibits Fas- and Tumor Necrosis Factor-induced Apoptosis

Cited by 302 publications

References 20 publications

Caspase Enzyme Activity Is Not Essential for Apoptosis During Thymocyte Development

Caspase Enzyme Activity Is Not Essential for Apoptosis During Thymocyte Development

Caspases: the executioners of apoptosis

Molecular Characteristics of Porcine Fas-associated Death Domain (FADD) and Procaspase-8

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