The cell-death machine

Chinnaiyan, Arul M.; Dixit, Vishva M.

doi:10.1016/s0960-9822(02)00541-9

Cited by 359 publications

(218 citation statements)

References 104 publications

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“…6,43,44 Our data are consistent with Z-VAD-fmk antagonized apoptosis in whole cells but was inactive in the cell-free system. The two other caspase inhibithis view as they show for the first time caspase 3 (CPP32/Yama/Apopain 4 ) cleavage in HL60 cells undergoing tors which are not cell-permeable were only tested in the cellfree system, and were also inactive against DNA fragmenapoptosis in response to camptothecin.…”

Section: Figuresupporting

confidence: 86%

“…Mch2␣ (caspase 6) 4 is also a member of the caspase subfamily closely related to CED-3. 6 As shown in Figure 4, lamin B was cleaved to a 32 kDa product in camptothecin-treated HL60 cells (Figure 4, lower panels). This cleavage was inhibited by Z-VAD-fmk (Figure 4, lower left panel).…”

mentioning

confidence: 76%

“…2,3 Asparate-specific cysteine proteases Drugs and chemicals (caspases) 4 play a central role in the execution phase of apoptosis. 5,6 The interleukin-1␤-converting enzyme (ICE) has Camptothecin was a generous gift from Drs ME Wall and MC been the first described homologue of the ced-3 death gene Wani (Research Triangle Park, NC, USA). It was freshly disproduct (CED-3) of Caenorhabditis elegans.…”

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confidence: 99%

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Camptothecin-induced apoptosis in p53-null human leukemia HL60 cells and their isolated nuclei: effects of the protease inhibitors Z-VAD-fmk and dichloroisocoumarin suggest an involvement of both caspases and serine proteases

Shimizu

Pommier

1997

Leukemia

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The human leukemia cell line, HL60 is very sensitive to various B can activate CPP32, 13 and apoptotic activation of proteaapoptotic stimuli and p53-null. The death-related cysteine prosome 14,15 and cathepsin D 16 have been reported. A nuclear teases of the caspases family play a central role in the scaffold protease has been postulated to activate apoptotic execution phase of apoptosis, and we recently reported the nuclease(s). 17 Our previous studies in human leukemia HL60 importance of serine protease activation in camptothecincells also indicated that apoptotic DNA fragmentation can be induced apoptotic endonuclease activation in HL60 cells. In the present study, we investigated the role of caspases (ICE/CEDinduced by serine proteases in a cell-free system and sup-3-related cysteine proteases) and serine proteases in cell death pressed by serine protease inhibitors. 18,19 induced by the topoisomerase I inhibitor, camptothecin, inThe goal of the present study was to investigate the effects HL60 cells and in a cell-free system. We found that CPP32 is of two cell-permeable protease inhibitors on camptothecin- also be used in a cell-free system. 18,32 In the present report, in a cell-free system. DCI also inhibited CPP32 cleavage. Taken together, these results suggest that in HL60 cells, both CPP32we demonstrate that CPP32 is proteolytically activated in and serine proteases are activated in camptothecin-induced response to camptothecin-induced apoptosis in HL60 cells. apoptosis. Activation of CPP32 requires both caspase and serine proteaseKeywords: camptothecin; topoisomerase I; apoptosis; caspase;activation. Furthermore, we show that in a cell-free system, serine protease; HL60only serine protease inhibitors block DNA fragmentation and lamin B degradation. These results suggest that serine proteases can function both downstream and upstream of the Introduction CPP32 activation step in a cell death pathway.Apoptosis is well defined morphologically 1 and recent studies indicate that a number of evolutionary conserved genes reguMaterials and methods late a common cell death pathway that is conserved from worms to humans. 2,3 Asparate-specific cysteine proteases Drugs and chemicals (caspases) 4 play a central role in the execution phase of apoptosis. 5,6 The interleukin-1␤-converting enzyme (ICE) has Camptothecin was a generous gift from Drs ME Wall and MC been the first described homologue of the ced-3 death gene Wani (Research Triangle Park, NC, USA). It was freshly disproduct (CED-3) of Caenorhabditis elegans. 7 Other members solved in dimethyl sulfoxide at 10 mM and further diluted in of the caspase family including caspase 3 (CPP32/Yama/ water before each experiment. The caspase inhibitor, N-benApopain) 8,9 have been identified and recent evidence suggests zyloxycarbony-Val-Ala-Asp(O-methyl)-fluoromethyketone (Zthat several caspases can be activated sequentially in the same VAD-fmk), and the serine protease inhibitor, 3,4-dichloroisoapoptotic cell. 10 Poly(ADP-ribose)polymerase (PARP) 8,9 and coumarin (...

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Section: Figuresupporting

confidence: 86%

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confidence: 76%

mentioning

confidence: 99%

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Camptothecin-induced apoptosis in p53-null human leukemia HL60 cells and their isolated nuclei: effects of the protease inhibitors Z-VAD-fmk and dichloroisocoumarin suggest an involvement of both caspases and serine proteases

Shimizu

Pommier

1997

Leukemia

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“…The dying cell degrades into subcellular membrane-bound vesicles called apoptotic bodies, which are ultimately removed by phagocytosis. Apoptosis is a molecular suicide program that is characterized by cytoplasmic shrinkage, nuclear condensation, and DNA fragmentation into 200-base pair fragments (Kerr et al, 1972;Cohen, 1993;Clarke and Clarke, 1995;Chinnaiyan and Dixit, 1996). It is a genetically regulated mechanism and its deregulation can result in multistep carcinogenesis (McDonnell and Korsmeyer, 1991;Thompson, 1995;Gilmore et al, 1996) Apoptosis is brought about by activation of a family of proteins known as caspases (cysteinyl, aspartate-specific proteases) (Cohen, 1997;Green, 2000).…”

Section: Mechanism Of Apoptosismentioning

confidence: 99%

Nuclear Factor-κB Activation: A Question of Life or Death

Shishodia¹,

Aggarwal²

2002

BMB Reports

204

167

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Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-κB activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-κB and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which may or may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-κB controls apoptosis.

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“…The first identified mammalian homolog of CED-3 was interleukin-lß-converting enzyme (ICE [7,8]), a cysteine protease which processes inactive prointerleukin-lß (pIL-lß) to its biologically active form [9]. Recently, several human (h) and murine (m) ICE or caspase (CASP) homologs have been cloned [10][11][12]. In the human system, CASP-1 (ICE [13]), CASP-2 (Ichl [14]), CASP-3 (CPP32, Yama or apopain [15][16][17]), CASP-4 (TX, Ich2 or ICE rcl -II [18][19][20]), CASP-5 (ICE rd -III or TY [20,21]), CASP-6 (Mch2 [22]), CASP-7 (Mch3, ICE-LAP3 or CMH-1 [23][24][25]), CASP-8 (MACH, FLICE or Mch5 [26][27][28]), CASP-9 (ICE-LAP6 [29]) and CASP-10 (Mch4 [26]) were identified.…”

Section: Introductionmentioning

confidence: 99%

Characterization of seven murine caspase family members

et al. 1997

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Seven members of the murine caspase (mCASP) family were cloned and functionally characterized by transient overexpression: mCASP-1 (mICE), mCASP-2 (Ichl), mCASP-3 (CPP32), mCASP-6 (Mch2), mCASP-7 (Mch3), mCASP-11 (TX) and mCASP-12. mCASP-11 is presumably the murine homolog of human CASP-4. Although mCASP-12 is related to human CASP-5 (ICE re i-III), it is most probably a new CASP-1 family member. On the basis of sequence homology, the caspases can be divided into three subfamilies: first, mCASP-1, mCASP-11 and mCASP-12; second, mCASP-2; third, mCASP-3, mCASP-6 and mCASP-7. The tissue distribution of the CASP-1 subfamily transcripts is more restricted than that of the CASP-3 subfamily transcripts, suggesting that the transcriptional regulation of the CASP members within one subfamily is related, but is quite different between the CASP-1 and the CASP-3 subfamilies. Transient overexpression of each of the seven CASPs induced apoptosis in mammalian cells. Only two, mCASP-1 as well as mCASP-3, were able to process precursor interleukin (IL)-lß to biologically active IL-lß. In addition, mCASP-3 is the predominant PARP-cleaving enzyme in vivo.

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The cell-death machine

Cited by 359 publications

References 104 publications

Camptothecin-induced apoptosis in p53-null human leukemia HL60 cells and their isolated nuclei: effects of the protease inhibitors Z-VAD-fmk and dichloroisocoumarin suggest an involvement of both caspases and serine proteases

Camptothecin-induced apoptosis in p53-null human leukemia HL60 cells and their isolated nuclei: effects of the protease inhibitors Z-VAD-fmk and dichloroisocoumarin suggest an involvement of both caspases and serine proteases

Nuclear Factor-κB Activation: A Question of Life or Death

Characterization of seven murine caspase family members

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