A cytosolic factor is required for mitochondrial cytochrome c efflux during apoptosis

Han, Zhiyong; Li, Gang; Bremner, Theodore A.; Lange, Thilo S.; Zhang, Guohong; Jemmerson, Ronald; Wyche, James H.; Hendrickson, Eric A.

doi:10.1038/sj.cdd.4400367

Cited by 23 publications

(25 citation statements)

References 35 publications

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“…Using this assay, we observed that treatment of HL-60 cells with the potent apoptosis inducer staurosporine (STS) induced a cytosolic activity, termed Cif (cytochrome c efflux-inducing factor), which rapidly facilitated cytochrome c efflux from purified mitochondria (17). Similar factors and activities have also been described by others (27,53).…”

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confidence: 51%

“…We recently developed a cell-free assay for studying regulation of mitochondrial cytochrome c efflux (17). Using this assay, we observed that treatment of HL-60 cells with the potent apoptosis inducer staurosporine (STS) induced a cytosolic activity, termed Cif (cytochrome c efflux-inducing factor), which rapidly facilitated cytochrome c efflux from purified mitochondria (17).…”

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confidence: 99%

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Cif (Cytochrome c Efflux-Inducing Factor) Activity Is Regulated by Bcl-2 and Caspases and Correlates with the Activation of Bid

Han

Bhalla

Pantazis

et al. 1999

Molecular and Cellular Biology

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The cytosolic factor Cif (cytochrome c-efflux inducing factor) was activated by the apoptosis inducers staurosporine and anti-Fas antibodies and rapidly induced the efflux of cytochrome c from purified human mitochondria. HL-60 cells that stably overexpressed a bcl-2 cDNA transgene (Bcl-2:HL-60 cells) contained mitochondria and a cytosol that were resistant to exogenous Cif and that lacked detectable endogenous Cif activity, respectively. Therefore, Bcl-2 overexpression negated Cif activity and suggested that the requirement for Cif resides upstream of Bcl-2 on the apoptotic signal transduction pathway. The addition of purified caspase 3, caspase 7, or caspase 8 to the cytosolic extract from Bcl-2:HL-60 cells, however, restored Cif activity, demonstrating that the inhibition of Cif by Bcl-2 overexpression could be overcome by activated caspases. Moreover, the addition of purified caspases to cytosolic extracts prepared from parental HL-60 cells was also sufficient to cause Cif activation, suggesting that caspases might be required for Cif activation. Consistent with these observations, Fas-induced apoptosis in Jurkat cells resulted in caspase 8 activation and subsequently in activation of Cif. Finally, we demonstrate that the activation of Cif correlated with the activation of the Bcl-2 family member Bid by caspases and that Cif activity was selectively neutralized by anti-Bid antibodies. Taken together, these results indicate that Cif is identical to Bid and that it can be inhibited by Bcl-2 and activated by caspases. Thus, Cif (Bid) is an important biological regulator for the transduction of apoptotic signals.

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confidence: 51%

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confidence: 99%

Cif (Cytochrome c Efflux-Inducing Factor) Activity Is Regulated by Bcl-2 and Caspases and Correlates with the Activation of Bid

Han

Bhalla

Pantazis

et al. 1999

Molecular and Cellular Biology

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“…Mitochondrial and cytosolic fractions were prepared as described (31). In brief, cells (5 ϫ 10 7 ) were incubated for 10 min on ice in 0.2 ml of a lysis buffer containing 10 mM Hepes-NaOH (pH 7.4), 5 mM MgCl 2 , 5 mM dithiothreitol, 1 mM phenylmethylsulfonyl fluoride, as well as leupeptin, aprotinin, and antipain each at 50 g/ml.…”

Section: Methodsmentioning

confidence: 99%

“…We next examined whether the IR-induced activation of caspase-9 in AT4BIVA and AT5BIVA cells is mediated by the release of mitochondrial cytochrome c. A cytosolic fraction was prepared from irradiated cells under conditions that maintain the integrity of mitochondria (31). Immunoblot analysis of this fraction revealed that the basal amounts of cytochrome c in AT cells were similar to each other and greater than that in control Lysates were subjected to immunoblot analysis with antibodies to PARP, which detect both the 116-kDa intact protein (arrow) and an 89-kDa cleavage product (arrowhead).…”

Section: Effects Of Ir On the Abundance Of Bcl-2 And Bax And Onmentioning

confidence: 99%

Ionizing Radiation-induced Apoptosis in Ataxia-Telangiectasia Fibroblasts

Zhang

Dimtchev

Dritschilo

et al. 2001

Journal of Biological Chemistry

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Ionizing radiation (IR) has been shown to induce apoptosis to a greater extent in a fibroblast cell line AT5BIVA derived from an individual with ataxia-telangiectasia (AT) than in control fibroblasts. However, the signaling pathway that underlies IR-induced apoptosis in AT cells has remained unknown. The mechanism of apoptosis in response to ␥-irradiation has now been examined in three AT fibroblast lines (AT3BIVA, AT4BIVA, and AT5BIVA) derived from different individuals with AT. The apoptotic indexes of these cell lines at 72 h after irradiation were 12, 31, and 35%, respectively, compared with a value of 2.3% for control fibroblasts. Immunoblot analysis and fluorometric assays revealed that the extents of IR-induced activation of caspase-3 and caspase-9 were markedly greater in AT4BIVA and AT5BIVA cells than in AT3BIVA and control cells.

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“…Cells were fractionated as described (Han et al, 1998a) and the cell lysate was divided into two equal volumes. One volume was used to isolate nuclei and mitochondria by mixing with 30 volumes of lysis buer containing 0.25 M sucrose.…”

Section: Fractionation Of Cellsmentioning

confidence: 99%

Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak

Chatterjee

Pantazis

et al. 2000

Oncogene

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A cytosolic factor is required for mitochondrial cytochrome c efflux during apoptosis

Cited by 23 publications

References 35 publications

Cif (Cytochrome c Efflux-Inducing Factor) Activity Is Regulated by Bcl-2 and Caspases and Correlates with the Activation of Bid

Cif (Cytochrome c Efflux-Inducing Factor) Activity Is Regulated by Bcl-2 and Caspases and Correlates with the Activation of Bid

Ionizing Radiation-induced Apoptosis in Ataxia-Telangiectasia Fibroblasts

Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak

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