Actin Cytoskeleton Is Required for Early Apoptosis Signaling Induced by Anti-Fas Antibody but Not Fas Ligand in Murine B Lymphoma A20 Cells

Bando, Masashige; Miyake, Yoshihiro; Shiina, Masashi; Wachi, Masaaki; Nagai, Kazuo; Kataoka, Takao

doi:10.1006/bbrc.2001.6199

Cited by 26 publications

(24 citation statements)

References 19 publications

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“…DISCUSSION Bioprobes are low molecular weight chemical inhibitors that can be used for the functional analysis of complex cellular processes (28). To date, various bioprobes that are able to modulate apoptosis have been reported (21,29). Caspase substrate-mimicking peptide inhibitors have been most frequently used to block apoptosis.…”

Section: Ech Preferentially Binds To Pro-caspase-8 In Intactmentioning

confidence: 99%

“…Functional and structural analyses of these regulators have contributed to our understanding of the molecular basis of Fas-mediated apoptosis. However, several non-peptide small molecules that modulate apoptosis also have been reported (15)(16)(17)(18)(19)(20)(21). These molecules are useful for dissecting the apoptosis signal transduction pathway and also may be potential candidates for therapeutic use.…”

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confidence: 99%

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Epoxycyclohexenone Inhibits Fas-mediated Apoptosis by Blocking Activation of Pro-caspase-8 in the Death-inducing Signaling Complex

Miyake¹,

Kakeya²,

Kataoka³

et al. 2003

Journal of Biological Chemistry

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Death receptors belong to the tumor necrosis factor receptor family. They can induce apoptosis following engagement with specific ligands and are known to play an important role in the regulation of the immune system. Here we report that epoxycyclohexenone (ECH) inhibits apoptosis induced by anti-Fas antibody, Fas ligand (FasL), or tumor necrosis factor-␣ but not by staurosporine, MG-132, C2-ceramide, or UV irradiation. These results suggest that ECH specifically blocks death receptor-mediated apoptosis. Neither the surface expression of Fas nor the Fas-FasL interaction was influenced by ECH. However, ECH did block the activation of pro-caspase-8 in the death-inducing signaling complex, although recruitment of Fas-associating death domain (FADD) and pro-caspase-8 was not affected. ECH inhibited the enzymatic activity of recombinant active caspase-8 at slightly lower concentrations than it did for active caspase-3 and active caspase-9 in vitro. However, in FasL-treated cells, ECH was only able to inhibit the activation of pro-caspase-8, and it had no effect on the already activated caspase-8 at a concentration that is effective at inhibiting Fas-induced apoptosis. ECH directly bound the large subunit of active caspase-8 that contains the active center cysteine and had a relatively higher affinity to pro-caspase-8. Moreover, compared with pro-caspase-3 and pro-caspase-9, pro-caspase-8 was predominantly depleted by biotinylated ECH with avidin beads in the cell lysates, suggesting that ECH preferentially affects pro-caspase-8. Thus, our results suggest that ECH blocks the self-activation of pro-caspase-8 in the death-inducing signaling complex and thus selectively inhibits death receptor-mediated apoptosis.

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Section: Ech Preferentially Binds To Pro-caspase-8 In Intactmentioning

confidence: 99%

mentioning

confidence: 99%

Epoxycyclohexenone Inhibits Fas-mediated Apoptosis by Blocking Activation of Pro-caspase-8 in the Death-inducing Signaling Complex

Miyake¹,

Kakeya²,

Kataoka³

et al. 2003

Journal of Biological Chemistry

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“…Many reports also suggest that ERM proteins regulate the initial phase of apoptosis through their effects on the actin cytoskeleton rearrangement. Indeed, it has been demonstrated that formation of blebs and disruption of nuclear integrity during apoptosis requires an intact actin cytoskeleton, and that actin accumulates at the basis of the apoptotic bodies [25]. All these studies together suggest that membrane receptors, actin cross-linker proteins and cytoskeleton remodeling are tightly regulated and implicated in the control of the cell's fate.…”

Section: Introductionmentioning

confidence: 99%

“…Actin stabilization and destabilization have both been shown to be implicated in regulation of apoptosis [23][24][25]. Many reports also suggest that ERM proteins regulate the initial phase of apoptosis through their effects on the actin cytoskeleton rearrangement.…”

Section: Introductionmentioning

confidence: 99%

The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells

et al. 2007

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The transmembrane receptor CD44 conveys important signals from the extracellular microenvironment to the cytoplasm, a phenomena known as ''outside-in'' signaling. CD44 exists as several isoforms that result from alternative splicing, which differ only in the extracellular domain but yet exhibit different activities. CD44 is a binding partner for the membrane-cytoskeleton cross-linker protein ezrin. In this study, we demonstrate that only CD44 standard (CD44s) colocalizes and interacts with the actin cross-linkers ezrin and moesin using well-characterized cell lines engineered to express different CD44 isoforms. Importantly, we also show that the association CD44s-ezrin-actin is an important modulator of Fas-mediated apoptosis. The results highlight a mechanism by which signals from the extracellular milieu regulate intracellular signaling activities involved in programmed cell death.

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“…Furthermore, the cytoskeletal network has been shown to modulate apoptosis either positively or negatively in different cell types (Huot et al, 1998;Korichneva and Hammerling, 1999;Posey and Bierer, 1999). For example, it was found that disruption of the actin cytoskeleton causes apoptosis in T cells (Suria et al, 1999) but it inhibits apoptosis in B lymphocytes (Melamed and Gelfand, 1999), lymphoma cells (Bando et al, 2002) and articular chondrocytes (Kim et al, 2003). Furthermore, regulators of actin filaments such as cofilin (Chua et al, 2003) and myosin light chain (Croft et al, 2005) have been implicated in the early phase of apoptosis and apoptotic nuclear disintegration, respectively.…”

Section: Introductionmentioning

confidence: 99%

BNIP-Sα induces cell rounding and apoptosis by displacing p50RhoGAP and facilitating RhoA activation via its unique motifs in the BNIP-2 and Cdc42GAP homology domain

2005

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Changes in cell morphology are linked to many cellular events including cytokinesis, differentiation, migration and apoptosis. We recently showed that BNIP-Sa induced cell rounding that leads to apoptosis via its BNIP-2 and Cdc42GAP Homology (BCH) domain, but the underlying mechanism has not been determined. Here, we have identified a unique region (amino acid 133-177) of the BNIP-Sa BCH domain that targets RhoA, but not Cdc42 or Rac1 and only the dominant-negative form of RhoA could prevent the resultant cell rounding and apoptotic effect. The RhoA-binding region consists of two parts; one region (residues 133-147) that shows some homology to part of the RhoA switch I region and an adjacent sequence (residues 148-177) that resembles the REM class I RhoAbinding motif. The sequence 133-147 is also necessary for its heterophilic interaction with the BCH domain of the Rho GTPase-activating protein, p50RhoGAP/ Cdc42GAP. These overlapping motifs allow tripartite competition such that overexpression of BNIP-Sa could reduce p50RhoGAP binding to RhoA and restore RhoA activation. Furthermore, BNIP-Sa mutants lacking the RhoA-binding motif completely failed to induce cell rounding and apoptosis. Therefore, via unique binding motifs within its BCH domain, BNIP-Sa could interact and activate RhoA while preventing its inhibition by p50RhoGAP. This concerted mechanism could allow effective propagation of the RhoA pathway for cell rounding and apoptosis.

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Actin Cytoskeleton Is Required for Early Apoptosis Signaling Induced by Anti-Fas Antibody but Not Fas Ligand in Murine B Lymphoma A20 Cells

Cited by 26 publications

References 19 publications

Epoxycyclohexenone Inhibits Fas-mediated Apoptosis by Blocking Activation of Pro-caspase-8 in the Death-inducing Signaling Complex

Epoxycyclohexenone Inhibits Fas-mediated Apoptosis by Blocking Activation of Pro-caspase-8 in the Death-inducing Signaling Complex

The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells

BNIP-Sα induces cell rounding and apoptosis by displacing p50RhoGAP and facilitating RhoA activation via its unique motifs in the BNIP-2 and Cdc42GAP homology domain

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