Role of mitochondria in apoptosis
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1 Special Review Series Biogenesis and Physiological Adaptation of Mitochondria General aspects of apoptosis Programmed cell death or apoptosis is an evolutionaryconserved mechanism employing a complex signalling machinery for the removal of cells. Removal of cells is important, for example, during development, organ homeostasis, and elimination of auto-reactive lymphocytes and neoplastic, damaged or infected cells. In general, stimuli triggering apoptosis can be separated into two groups, i.e. physiological and stress stimuli. Physiological stimuli include surface receptors such as TNF or CD95; examples of stress stimuli are UV light, irradiation, viral and bacterial infections, etc. While many physiological stimuli trigger death via surface receptors, the initiation of stress-induced apoptosis is much less defined, but seems to involve mitochondria at a very early stage of the intracellular signalling cascade. Receptor-induced apoptosis CD95 initiates apoptosis (Fig. 1) by a translocation of the acid sphingomyelinase from an intracellular compartment onto the cell membrane surface (Grassmé et al. 2001a,b). The cell membrane contains small distinct domains that are mainly composed of sphingolipids and cholesterol (Simons & Ikonen, 1997). Homo- and heterotypic interactions of sphingolipids and cholesterol render these domains less fluid than the other parts of the cell membrane and result in the separation of these small domains from phospholipids in the cell membrane Role of mitochondria in apoptosis Erich Gulbins *, Stephan Dreschers and Jürgen Bock Department of Molecular Biology, University of Essen, Hufelandstraße 55, Essen, Germany Apoptosis is an evolutionary-conserved physiological mechanism to remove cells from an organism. Cellular apoptosis is mediated via an intracellular signalling programme that involves a variety of signalling molecules and cellular organelles including caspases, sphingomyelinases, Bcl-2-like proteins and proteins to cleave the DNA and mitochondria. Mitochondria contain several pro-apoptotic molecules that activate cytosolic proteins to execute apoptosis, block anti-apoptotic proteins in the cytosol and directly cleave nuclear DNA. Mitochondria trap these pro-apoptotic proteins and physically separate pro-apoptotic proteins from their cytoplasmic targets. Apoptosis is then initiated by the release of mitochondrial pro-apoptotic proteins into the cytosol. This process seems to be regulated by Bcl-2-like proteins and several ion channels, in particular the permeability transition pore (PTP) that is activated by almost all pro-apoptotic stimuli. Experimental Physiology (2003) 88.1, (Simons & Ikonen, 1997). These domains that are also named rafts are transformed by acid sphingomyelinasereleased ceramide: ceramide triggers a fusion of many small raft domains to a large platform (Grassmé et al. 2001a,b) that serves to cluster CD95, an event required for the initiation of specific CD95 signalling (Grassmé et al. 2001a). Clustered CD95 efficiently recruits an adapter protein, Fas-associated death domain (FADD), that binds to a protease, caspase 8 (Boldin et al. 1996; Muzio et al. 1996). Caspases are a family of cysteine proteases that cleave their substrates specifically after aspartate residues (for review see Green & Kroemer, 1998). They are synthesized as inactive pro-enzymes that are converted to catalytically active proteases by limited proteolysis (Green & Kroemer, 1998). Caspase 8 transfers the apoptotic signal from CD95 via Bcl-2-like proteins (see below) and unknown mechanisms to mitochondria or directly to further caspases, in particular caspase 3. This caspase serves to execute apoptosis by cleavage of a large number of intracellular proteins, including enzymes involved in genome function, regulators of cell-cycle progression and structural proteins of the nucleus and cytoskeleton (Green & Kroemer, 1998). Cleavage of these proteins results in morphological alterations indicative of apoptosis, e.g. membrane-blebbing and DNA-fragmentation (Green & Kroemer, 1998). In summary, these receptor-initiated signalling pathways seem to employ mitochondria primarily to enhance the apoptotic signal. Publication of The Physiological Society * Corresponding author: erich.gulbins@uni-essen.de 2503
2 86 E. Gulbins, S. Dreschers and J. Bock Exp Physiol 88.1 Stress-induced apoptosis In contrast, much less is known about the initiation of stress-induced apoptosis (Fig. 1). Many stress stimuli seem to trigger apoptosis at or immediately upstream of mitochondria. A recent publication (Lassus et al. 2002) indicated an important role of caspase 2 upstream of mitochondria in the mediation of apoptosis upon cytotoxic stress. Further, Bcl-2-like proteins seem to be central in the transfer of the apoptotic signal to mitochondria during stress-induced apoptosis. The prosurvival or pro-apoptotic properties, respectively, and the number of Bcl-2 homology domains (BH1 4) characterize Bcl-2 family proteins (Kelekar & Thompson, 1998; Adams & Cory, 2001). Members of the pro-survival group include Bcl-2, Bcl-xL, Bcl-w, Mcl-1, Boo/Diva, A1/Bfl-1. Some virus-coded proteins, e.g. E1B19K (Huang et al. 1997) and BHRF1 (Dawson et al. 1998), are homologous to Bcl-2 and also prevent apoptosis. Pro-apoptotic proteins are Bax, Bak, Bok and a subgroup of Bcl-2 like proteins which contain only BH3 domains, the BH3-only proteins, i.e. Bad, Bim, Bmf, Bid, Noxa, Puma (Huang & Strasser, 2000). Although it is unknown how Bcl-2-like proteins trigger apoptosis, it has been shown that the multidomain pro-apoptotic members, Bax or Bak, are central for the induction of mitochondrial dysfunction during apoptosis (Adams & Cory, 2001). Bcl-2-like proteins appear to be regulated by a variety of mechanisms including the association of Bcl-2 and Bcl-xL with Bax or BH-3-only molecules (Kelekar & Thompson, 1998; Adams & Cory, 2001), which sequesters the pro-apoptotic proteins and, thus, blocks apoptosis. Similar mechanisms seem to be involved in the regulation of Bcl-2-like proteins by the association with proteins (Zha et al. 1996), the interaction of Bim with dynein (Puthalakath et al. 1999), Bmf binding to the actin cytoskeleton (Puthalakath et al. 2001) and binding of phosphorylated Bad to lipid rafts (Ayllon et al. 2002). Further, phosphorylation/dephosphorylation events mediated by a protein kinase B/Akt (PKB/Akt) signalling pathway have been shown to regulate the activity of Bcl-2-like proteins (Del Peso et al. 1997). Different apoptotic stimuli seem to recruit a different set of Bcl-2-like proteins. For instance, CD95 and TNF trigger the cleavage and activation of Bid (Luo et al. 1998). Active Bid induces a conformational change and oligomerization of Bax that finally results in the insertion of Bax in the outer mitochondrial membrane (Desagher et al. 1999; Murphy et al. 2000). In contrast, growth factor withdrawal leads to a dephosphorylation and limited proteolysis of Bad that mediates apoptosis (Kim et al. 2002). Apoptosis induced by etoposide or staurosporine triggers an N-terminal cleavage of Bax resulting in an 18 kda fragment which promotes cell death (Gao & Dou, 2000). Activation of the devil release of pro-apoptotic factors from mitochondria Many pro-apoptotic signals converge at mitochondria and most, if not all, of these stimuli trigger a change of the mitochondrial membrane permeability resulting in the release of several mitochondrial proteins into the cytoplasm, which constitutes the key event of mitochondriamediated apoptosis. Thus, mitochondria might be described as organelles that serve as a gatekeeper to trap a variety of pro-apoptotic proteins and prevent the function of these proteins in the cytosol. The release of the proteins into the cytosol induces apoptosis. Pro-apoptotic proteins released Figure 1 Pathways leading to apoptosis. Apoptosis initiated by receptor molecules or by intracellular or extracellular stress merges at the level of mitochondria. Key molecules integrating apoptotic stimuli to mitochondria seem to be Bcl-2-like proteins. The release of pro-apoptotic molecules from mitochondria triggers apoptosis.
3 Exp Physiol 88.1 Mitochondrial apoptosis 87 from mitochondria during apoptosis include: (a) cytochrome c (Liu et al. 1996), (b) caspase 9 (Susin et al. 1999a), (c) the protein named second mitochondrial activator of caspases (Smac)/direct inhibitor of apoptosis proteins binding protein with low pi (DIABLO) (Verhagen et al. 2000; Du et al. 2000), (d) apoptosis-inducing factor (AIF) (Zamzani et al. 1996), (e) high temperature-requiring proteins (HtrA2) (Suzuki et al. 2001), (f) endonuclease G (Li et al. 2001). The release of these proteins is caused by a marked increase of the permeability of the outer mitochondrial membrane and, at least in part, also of the inner mitochondrial membrane. The molecular details of the permeability change are discussed below. While cytochrome c, caspase 9 and Smac/DIABLO seem to be involved in almost all forms of mitochondria-induced apoptosis, AIF, HtrA2 and endonuclease G seem to have a specialized role in apoptosis (Fig. 2). Cytochrome c. Cytochrome c localizes to the mitochondrial intermembrane space and the increase of the outer mitochondrial membrane permeability permits the release of cytochrome c into the cytoplasm (Liu et al. 1996). Cytosolic cytochrome c initiates the formation of a multiprotein complex composed of apoptotic proteaseactivating factor (APAF-1), datp and caspase 9 (Liu et al. 1996; Zhou et al. 1997). This complex has been termed apoptosome. The autocatalytic maturation of caspase 9 in the complex and/or the allosteric activation of caspase 9 by APAF-1 binding finally results in the cleavage of caspase 3 and, thus, the activation of the execution phase of apoptosis. IAPs, DIABLO/Smac and caspase 9. The activity of caspase 9 (and other caspases) is suppressed by inhibitors of apoptosis (IAPs) (Crook et al. 1993) and to achieve apoptosis the function of these proteins must be suppressed. IAP proteins contain one or several baculovirus IAP repeat (BIR) domains that are central for the inhibition of caspase activity (Crook et al. 1993). To permit induction of apoptosis by the apoptosome, i.e. the complex of cytochrome c, datp, caspase 9 and APAF-1, the inhibitory function of IAPs needs to be released. This function is mediated by Smac/DIABLO, a protein that also localizes to the mitochondrial intermembrane space (Verhagen et al. 2000; Du et al. 2000). Upon release of Smac/DIABLO into the cytosol triggered by apoptotic stimuli, the protein interacts with IAP proteins, preferably with the BIR domains of IAPs. This releases caspases and permits the activity of these proteases to promote apoptosis. AIF, HtrA2 and endonuclease G further factors released by mitochondria during apoptosis. HtrA2/Omi, a serine protease residing in the mitochondrial intermembrane space in normal cells, neutralizes IAPs upon release into the cytosol and, thus, permits the activity of caspases (Suzuki et al. 2001). In addition, HtrA2/Omi triggers an unusual form of apoptosis without apoptotic body formation that seems to be mediated by the serine protease activity and is independent of caspase 9 and APAF-1 (Hegde et al. 2002). Figure 2 Role of mitochondria in apoptosis. Mitochondria release several pro-apoptotic factors upon induction of apoptosis. These factors are either directly triggering apoptosis by associating with cytosolic factors to form the apoptosome or they neutralize cytosolic proteins that inhibit apoptosis. Finally, some mitochondrial, pro-apoptotic proteins translocate into the nucleus to induce DNA fragmentation.
4 88 E. Gulbins, S. Dreschers and J. Bock Exp Physiol 88.1 While all the proteins described above directly form or promote the formation of the apoptosome, mitochondria also release some proteins upon induction of apoptosis that directly act in the nucleus to induce DNA cleavage and oligonucleosomal DNA breakage. Those proteins include the apoptosis-inducing factor (AIF) (Zamzani et al. 1996) and endonuclease G (Li et al. 2001). The release of AIF from the mitochondrial intermembrane space into the cytosol is initiated by a cleavage of the N-terminal part of AIF that contains a mitochondrial localization sequence. Translocation of AIF into the nucleus seems to be mediated by the C-terminal part of the protein that contains two putative nuclear localization elements (Susin et al. 1999b). AIF induces high molecular weight DNA fragmentation and chromatin condensation. However, cytosolic AIF also triggers a depolarization of the mitochondrial membrane or changes in the cell membrane, e.g. translocation of phosphatidylserine (Susin et al. 2000). It is of note that all these effects of AIF are independent of caspases, Bcl-2 or APAF-1. Regulating the devil mechanisms controlling the release of pro-apoptotic factors from mitochondria The mechanisms mediating the release of pro-apoptotic factors from mitochondria are still largely unknown. However, numerous studies showed a central role of the permeability transition pore (PTP) protein complex. Activation of this ion channel complex triggers mitochondrial membrane permeabilization that finally results in an increased permeability of the outer mitochondrial membrane even for proteins and of the inner mitochondrial membrane at least for low molecular weight ions (Zamzani & Kroemer, 2001). The inner mitochondrial membrane permeability leads to a depolarization of the mitochondrial membrane potential. The PTP mainly consists of the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane and the adenine nucleotide translocase (ANT) in the inner mitochondrial membrane (Zamzani & Kroemer, 2001). Several studies suggested that upon induction of apoptosis pro-apoptotic Bcl-2-like proteins, e.g. Bax, interact with components of the PTP, in particular VDAC and ANT, to form a large pore permitting the release of cytochrome c and other pro-apoptotic proteins, while anti-apoptotic proteins prevent the opening of the PTP (Narita et al. 1998; Shimizu et al. 1998, 1999, 2000; Marzo et al. 1998). Opening of the PTP also results in a flux of ions and water into the mitochondria that mediates swelling of the mitochondria and, eventually, a rupture of the outer mitochondrial membrane (Van der Heiden et al. 1997). Mechanisms mediating PTP activation are still not clarified. Some studies suggested that the association of Bax with VDAC results in an increase of VDAC conductance (Shimizu et al. 2000). However, other studies indicated that interaction of Bax with VDAC inhibits VDAC triggering an inhibition of the ADP/ATP exchange between mitochondria and the cytosol (Van der Heiden et al. 1997, 2000). The disturbance of the energy balance in the cell finally results in increased permeability of the mitochondrial outer membrane, release of cytochrome c and the opening of the PTP (Van der Heiden et al. 2000, 2001). In addition, Bcl-2-like proteins might form pores independently of the PTP, since they seem able to oligomerize to ion channel structures at least in liposomes and isolated mitochondria (Korsmeyer et al. 2000). Whether this or some other mechanism, e.g. the formation of ceramide-mediated ion channels (Siskind et al. 2002), contributes to the release of pro-apoptotic proteins from mitochondria in vivo has yet to be determined. We have recently identified a novel mitochondrial potassium channel termed Kv1.3 that seems to be critical for the induction of apoptosis at least by ceramide, staurosporine and TNF (A. Jekle, J. Szabo, J. Bock, C. Adams, V. Jendrossek, A. Riehle, F. Lang, M. Zoretti & E. Gulbins, in preparation). Whether this ion channel interacts with Bcl- 2-like proteins or even forms a novel ion channel identity by association with these proteins remains to be determined. The release of several pro-apoptotic factors from mitochondria and the interaction with Bcl-2-like proteins place mitochondria in the centre of apoptosis regulation. Although many details of mitochondrial functions in apoptosis have been identified, it is still unknown how the signals from pro-apoptotic stimuli and receptors are transmitted to mitochondria. Even more importantly, the molecular details of apoptosis regulation by Bcl-2-like proteins at the level of mitochondria are elusive. These proteins and interactions might be very interesting targets for the development of new strategies to treat degenerative disorders and cancer. Adams JM & Cory S (2001). Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci 26, Ayllon V, Fleischer A, Cayla X, Garcia A & Rebollo A (2002). Segregation of Bad from lipid rafts is implicated in the induction of apoptosis. J Immunol 168, Boldin MP, Goncharov TM, Goltsev YV & Wallach D (1996). Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85, Crook NE, Clem RJ & Miller LK (1993). An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol 67, Dawson CW, Dawson J, Jones R, Ward K & Young LS (1998). Functional differences between BHRF1, the Epstein-Barr virusencoded Bcl-2 homologue, and Bcl-2 in human epithelial cells. J Virol 72, Del Peso L, Gonzalez-Garcia M, Page C, Herrera R & Nunez G (1997). Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 278, Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Lauper S, Maundrell K, Antonsson B & Martinou JC (1999). Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 144,
5 Exp Physiol 88.1 Mitochondrial apoptosis 89 Du C, Fang M, Li Y, Li L & Wang X (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, Gao G & Dou QP (2000). N-terminal cleavage of Bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes Bcl-2-independent cytochrome C release and apoptotic cell death. J Cell Biochem 80, Grassmé H, Jekle A, Riehle A, Schwarz H, Berger J, Sandhoff K, Kolesnick R & Gulbins E (2001a). CD95 signaling via ceramide rich membrane rafts. J Biol Chem 276, Grassmé H, Schwarz H & Gulbins E (2001b). Surface ceramide mediates CD95 clustering. Biochem Biophys Res Commun 284, Green D & Kroemer G (1998). The central executioner of apoptosis: caspases or mitochondria? Trends Cell Biol 8, Hegde R, Srinivasula SM, Yhang Y, Wassell R, Mukattash R, Cilenti L, Dubois G, Layebnik Z, Yervos AS, Fernandey-Alnemri T & Alnemri ES (2002). Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts IAP-caspase interaction. J Biol Chem 277, Huang DC, Cory S & Strasser A (1997). Bcl-2, Bcl-XL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death. Oncogene 14, Huang DC & Strasser A (2000). BH3-only proteins essential initiators of apoptotic cell death. Cell 103, Kelekar A & Thompson CB (1998). Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8, Kim BC, Mamura M, Choi KS, Calabretta B & Kim SJ (2002). Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells. Mol Cell Biol 22, Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ & Schlesinger PH (2000). Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ 7, Lassus P, Opitz-Araya X & Lazebnik Y (2002). Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science 297, Li LY, Luo X & Wang X (2001). Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412, Liu XS, Kim CN, Yang J, Jemmerson R & Wang X (1996). Induction of apoptotic program in cell-free extracts: requirement for datp and cytochrome C. Cell 86, Luo X, Budihardjo I, Zou H, Slaughter C & Wang X (1998). Bid, a Bcl-2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94, Marzo I, Brenner C, Zamzami N, Jurgensmeier JM, Susin SA, Vieira HlA, Prevost MC, Xie Z, Matsuyama S, Reed JC & Kroemer G (1998). Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281, Murphy KM, Streips UN & Lock RB (2000). Bcl-2 inhibits a Fasinduced conformational change in the Bax N-terminus and Bax mitochondrial translocation. J Biol Chem 275, Muzio M, Chinnaiyan AM, Kischkel FC, O Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer P, Peter ME & Dixit VM (1996). FLICE, a novel FADDhomologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/Apo-I) death inducing signaling complex. Cell 85, Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H & Tsujimoto Y (1998). Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A 95, Puthalakath H, Huang DC, O Reilly LA, King SM & Strasser A (1999). The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell 3, Puthalakath H, Villunger A, O Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC & Strasser A (2001). Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 293, Shimizu S, Eguchi Y, Kamiike W, Funuhashi Y, Migon A, Lacronique V, Matsuda H & Tsujimoto Y (1998). Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux. Proc Natl Acad Sci USA 95, Shimizu S, Ide T, Yanagida T & Tsujimoto Y (2000). Electrophysiological study of a novel large pore formed by Bax and the voltage-dependent anion channel that is permeable to cytochrome c. J Biol Chem 275, Shimizu S, Narita M & Tsujimoto Y (1999). Bcl-2-family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 399, Simons K & Ikonen E (1997). Functional rafts in cell membranes. Nature 387, Siskind LJ, Kolesnick RN & Colombini M (2002). Ceramide channels increase the permeability of the mitochondrial outer membrane to small proteins. J Biol Chem 277, Susin SA, Daugas E, Ravagnan L, Samejima K, Zamzami N, Loeffler M, Costantini P, Ferri KF, Irinopoulou T, Prevost MC, Brothers G, Mak TW, Penninger J, Earnshaw WC & Kroemer G (2000). Two distinct pathways leading to nuclear apoptosis. J Exp Med 192, Susin SA, Lorenzo HK, Zamzani N, Marzo I, Larochette N, Alzari PM & Kroemer G (1999a). Mitochondrial release of caspase-2 and -9 during the apoptotic process. J Exp Med 189, Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM & Kroemer G (1999b). Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397, Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K & Takahashi R (2001). A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8, Van Der Heiden MG, Chandel NS, Li XX, Schumacker PT, Colimbini M & Thompson CB (2000). Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival. Proc Natl Acad Sci U S A 97, Van Der Heiden MG, Chandel NS, Williamson EK, Schumacker PT & Thompson CB (1997). Bcl-x(L) regulates the membrane potential and volume homeostasis of mitochondria. Cell 91, Van Der Heiden MG, Li XX, Gottleib E, Hill RB, Thompson CB & Colombini M (2001). Bcl-xL promotes the open configuration of the voltage-dependent anion channel and metabolite passage through the outer mitochondrial membrane. J Biol Chem 276,
6 90 E. Gulbins, S. Dreschers and J. Bock Exp Physiol 88.1 Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ & Vaux DL (2000). Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102, Zamzani N, Susin SA, Marchetti P, Hirsch T, Gomez-Monterrey I, Castedo M & Kroemer G (1996). Mitochondrial control of nuclear apoptosis. J Exp Med 183, Zamzani N & Kroemer G (2001). The mitochondrion in apoptosis: how Pandora s box opens. Nature Reviews 2, Zha J, Harada H, Yang E, Jockel J & Korsmeyer SJ (1996). Serine phosphorylation of death agonist BAD in response to survival factor results in binding to not BCL-X(L). Cell 87, Zhou H, Wenzel WJ, Liu X, Lutschg A & Wang XD (1997). Apaf-1, a human protein homologous to C. elegans Ced-4, participates in cytochrome c-dependent activation of caspase 3. Cell 90, Acknowledgements The authors were supported by DFG grant Gu /2 and the EU (MANAD).
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