Regulation of death receptor-mediated apoptosis pathways

Schmitz, Ingo; Kirchhoff, Sabine; Krammer, Peter H.

doi:10.1016/s1357-2725(00)00048-0

Cited by 235 publications

(164 citation statements)

References 134 publications

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“…Activation of caspase family members is at the core of apoptosis, representing a point of intersection of various apoptotic pathways. Tumour necrosis factor or Fas/CD95 receptors, mitochondrial proteins (such as cytochrome c) and granzyme are able to induce cell death through activation of the caspase cascade (Schmitz et al, 2000;Shi, 2002). Damage to or stress in the ER or Golgi has been shown to be able to trigger apoptosis (Herr and Debatin, 2001;Breckenridge et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Caspase family members are important factors in the induction of apoptosis triggered by various apoptotic stimuli (Schmitz et al, 2000;Shi, 2002). The activation of caspases involves a series of protein cleavages resulting in small, active fragments for initiating apoptosis (Thornberry et al, 1997;Bhornberry and Lazebnik, 1998).…”

Section: Different Susceptibilities Of Lncap and Pc3 Cells To Apoptosmentioning

confidence: 99%

“…Caspases, a highly conserved family of cysteine proteases, are key apoptotic effectors and play a critical role in apoptosis through a cascade of cleavage events (Schmitz et al, 2000;Shi, 2002). Caspases exist as dormant proenzymes in cells and are activated through proteolysis.…”

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confidence: 99%

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Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells

et al. 2007

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It is known that polysaccharides extracted from the Phellinus linteus (PL) mushroom possess antitumour activity. We previously have demonstrated that high doses of PL render murine or human lung cancer cells susceptible to apoptosis. However, the molecular mechanisms of PL-mediated apoptosis have not been fully explored. In this study, we demonstrate that LNCaP cells expressing the androgen receptor (AR) are highly susceptible to apoptosis in response to treatment with high doses of PL. In this process, caspase 8 and its downstream effectors (such as BID), as well as ER stress-related, apoptotic signalling, are activated. In contrast, a moderate amount of apoptosis occurs in PC3 cells (that lack AR) after the same treatment, which does not activate ER-mediated apoptotic signalling. We also show that, in the process of PL-induced apoptosis, caspase 2 is induced in LNCaP cells, but not in PC3 cells. However, LNCaP cells that express a mutated AR or LNCaP cells treated with a caspase 2 inhibitor blocked ER stress-induced apoptotic signals. The magnitudes of the induction of apoptosis in these cells are comparable with what occurred in the PC3 cells. The data demonstrate that high doses of PL activate the AR-dependent and independent apoptotic pathways. Our study also suggests that caspase 2 is a key target in the determination of the susceptibility of prostate cancer cells to PL-induced apoptosis. Phellinus linteus (PL) is among a number of well-known medicinal mushrooms from Asian countries, which have been taken orally since ancient times as a health-promoting dietary supplement and an adjuvant to combat viral and bacterial infections. PL, after purification, shows a relatively homogeneous molecular weight distribution on gel permeation HPLC and is estimated to be around 150 kDa from the retention time on HPLC pullulan molecular markers (Song et al, 1995). The main components of PL are polysaccharides (Song et al, 1995;Lorenzen and Anke, 1998;Borchers et al, 1999;Han et al, 1999). Many studies demonstrated that polysaccharides from various substances, including PL, are remarkably effective in inhibiting the growth of tumours without toxic side effects. Studies also showed that polysaccharides in PL are able to suppress tumours, either indirectly by enhancing the host's immune system or directly by inducing apoptosis in tumour cells (Chihara et al, 1969;Chung et al, 1982;Cun et al, 1994;Wasser, 2002;Collins et al, 2006;Guo et al, 2006). Therefore, the antitumour, antiangiogenic and immunomodulatory effects of PL are potential areas for developing novel pharmaceutical products. However, the underlying molecular mechanisms of the antitumour effects of PL have not yet been fully explored.Changes in the androgen receptor (AR) have been indicated to contribute to the development of prostate cancer and are a serious challenge to effective treatment. Mutations in the AR can increase its affinity for ligand binding, permitting activation by nonandrogenic hormones or even antagonists (Nelson et al, 2003;Debes and Tindall, ...

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Section: Discussionmentioning

confidence: 99%

Section: Different Susceptibilities Of Lncap and Pc3 Cells To Apoptosmentioning

confidence: 99%

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Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells

et al. 2007

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“…The extrinsic pathway involves the activation of receptors in the plasma membrane through the binding of ligands such as the Fas/CD95, TNFa and TRAIL. 10 This receptor activation ultimately leads to processes that cleave and activate the initiator procaspases 8 and/or 10 which in turn activate the executioner caspases 3 and/or 7. The executioner caspases are responsible for the appearance of late apoptosis markers such as DNA fragmentation and plasma membrane blebbing.…”

Section: Introductionmentioning

confidence: 99%

Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

2006

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Apoptosis is a phenomenon fundamental to higher eukaryotes and essential to mechanisms controlling tissue homeostasis. Bcl-2 family proteins tightly control this cell death program by regulating the permeabilization of the mitochondrial outer membrane and, hence, the release of cytochrome c and other proapoptotic factors. Mitochondrial apoptosisinduced channel (MAC) is the mitochondrial apoptosisinduced channel and is responsible for cytochrome c release early in apoptosis. MAC activity is detected by patch clamping mitochondria at the time of cytochrome c release. The Bcl-2 family proteins regulate apoptosis by controlling the formation of MAC. Depending on cell type and apoptotic inducer, Bax and/or Bak are structural component(s) of MAC. Overexpression of the antiapoptotic protein Bcl-2 eliminates MAC activity. The focus of this review is a biophysical characterization of MAC activity and its regulation by Bcl-2 family proteins, and ends with some discussion of therapeutic targets.

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“…[1][2][3][4][5] Death receptors contain an intracellular death domain (DD) that plays a central role in the transduction of the apoptotic signal. Crosslinking of CD95 with its natural ligand CD95L (CD178) 6 or with agonistic antibodies such as anti-APO-1 7 induces apoptosis in sensitive cells.…”

Section: Introductionmentioning

confidence: 99%

The role of CAP3 in CD95 signaling: new insights into the mechanism of procaspase-8 activation

et al. 2005

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Formation of the CD95 (APO-1/Fas) death inducing signaling complex (DISC) plays a central role in CD95 signaling. Previously, CD95 DISC composition was analyzed by twodimensional gel electrophoresis and four major cytotoxicityassociated proteins (CAP1-4) were found. CAP1 and CAP2 were defined to be unmodified and phosphorylated FADD, respectively. CAP4 was identified as procaspase-8a. CAP3, however, has remained elusive. In this study, we demonstrate that CAP3 is an intermediate of procaspase-8 processing. CAP3 is generated within seconds of DISC formation and subsequently processed to the prodomain of procaspase-8a that is known as p26 (CAP5). These findings lead to new insights into the mechanism of procaspase-8 processing and apoptosis initiation.

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Regulation of death receptor-mediated apoptosis pathways

Cited by 235 publications

References 134 publications

Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells

Phellinus linteus activates different pathways to induce apoptosis in prostate cancer cells

Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

The role of CAP3 in CD95 signaling: new insights into the mechanism of procaspase-8 activation

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