Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.

Quan, Long T.; Tewari, Muneesh; O’Rourke, Karen; Dixit, Vishva M.; Snipas, Scott J.; Poirier, Guy G.; Ray, Carol; Pickup, David J.; Salvesen, Guy S.

doi:10.1073/pnas.93.5.1972

Cited by 169 publications

(110 citation statements)

References 46 publications

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“…Caspase-3 knockout mice show a severe phenotype with early lethality due to failure of developmental programmed cell death of neuronal cell precursors, which argues for the central role of caspase-3 at least in neurons (15). Numerous groups described important roles of caspase-3 in various experimental systems (16,17). The substrate sequence DEVD is specific for caspases-3 and -7 (7).…”

Section: Resultsmentioning

confidence: 99%

Rhodamine 110-Linked Amino Acids and Peptides as Substrates To Measure Caspase Activity upon Apoptosis Induction in Intact Cells

Hug¹,

Łos²,

Hirt³

et al. 1999

Biochemistry

124

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Caspases (cysteine aspartate-specific proteases) are a structurally related group of cysteine proteases that cleave peptide bonds following specific recognition sequences. They play a central role in activating apoptosis of vertebrate cells. To measure apoptosis induced by various stimuli and at an early apoptotic stage, caspases are an ideal target. This is especially the case when apoptotic cells have to be analyzed ex vivo before phagocytes remove them. A new and sensitive caspase assay is based on a substrate that contains only aspartate residues linked to rhodamine 110. With this and similar substrates, we are able to detect intracellular caspase activation by flow cytometry after apoptosis induction in intact hematopoetic cell lines.

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Section: Resultsmentioning

confidence: 99%

Rhodamine 110-Linked Amino Acids and Peptides as Substrates To Measure Caspase Activity upon Apoptosis Induction in Intact Cells

Hug¹,

Łos²,

Hirt³

et al. 1999

Biochemistry

124

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“…After engagement of a target cell by CTL and granule exocytosis, grB is delivered to the target cell cytoplasm and nucleus in a perforin-dependent process (30 -32). grB, a serine protease, can cleave multiple substrates in the target cell (33)(34)(35)(36)(37), and triggers apoptosis. Activation of caspases is required for grB-induced nuclear DNA fragmentation, but not for the induction of cell death by grB, and it is clear that inhibition of caspases alone is insufficient to fully protect cells from grB (27,28).…”

Section: Discussionmentioning

confidence: 99%

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

Jerome

Chen

Lang

et al. 2001

The Journal of Immunology

108

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HSV-1 inhibits apoptosis of infected cells, presumably to ensure that the infected cell survives long enough to allow completion of viral replication. Because cytotoxic lymphocytes kill their targets via the induction of apoptosis, protection from apoptosis could constitute a mechanism of immune evasion for HSV. Several HSV genes are involved in the inhibition of apoptosis, including Us5, which encodes glycoprotein J (gJ). Viruses deleted for Us5 showed defects in inhibition of caspase activation after Fas ligation or UV irradiation. Transfected cells expressing the Us5 gene product gJ were protected from Fas- or UV-induced apoptosis, as measured by morphology, caspase activation, membrane permeability changes, or mitochondrial transmembrane potential. In contrast, caspase 3 activation in mitochondria-free cell lysates by granzyme (gr)B was inhibited equivalently by Us5 deletion and rescue viruses, suggesting that gJ is not required for HSV to inhibition this process. However, mitochondria-free lysates from transfected cells expressing Us5/gJ were protected from grB-induced caspase activation, suggesting that Us5/gJ is sufficient to inhibit this process. Transfected cells expressing Us5/gJ were also protected from death induced by incubation with purified grB and perforin. These findings suggest that HSV has a comprehensive set of immune evasion functions that antagonize both Fas ligand- and grB-mediated pathways of CTL-induced apoptosis. The understanding of HSV effects on killing by CTL effector mechanisms may shed light on the incomplete control of HSV infections by the immune system and may allow more rational approaches to the development of immune modulatory treatments for HSV infection.

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“…Granzyme B also exhibits an unusual specificity for Asp in the P " position. In itro, granzyme B can activate caspase-3, as assessed by formation of its p17 subunit as well as its ability to cleave PARP to its signature fragment [74,75]. Activation of caspase-3 by granzyme B is within the physiological range [75].…”

Section: Figure 3 Proenzyme Organization Of the Caspasesmentioning

confidence: 99%

“…In itro, granzyme B can activate caspase-3, as assessed by formation of its p17 subunit as well as its ability to cleave PARP to its signature fragment [74,75]. Activation of caspase-3 by granzyme B is within the physiological range [75]. While granzyme B can activate directly caspase-3, it may also cleave another caspase which in turn activates caspase-3.…”

Section: Figure 3 Proenzyme Organization Of the Caspasesmentioning

confidence: 99%

Caspases: the executioners of apoptosis

Cohen

1997

Biochemical Journal

4,323

2,952

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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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Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.

Abstract: The serine protease granzyme B, which is secreted by cytotoxic cells, is one

Cited by 169 publications

References 46 publications

Rhodamine 110-Linked Amino Acids and Peptides as Substrates To Measure Caspase Activity upon Apoptosis Induction in Intact Cells

Rhodamine 110-Linked Amino Acids and Peptides as Substrates To Measure Caspase Activity upon Apoptosis Induction in Intact Cells

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

Caspases: the executioners of apoptosis

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