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PubMedDate not supplied

Caspase 10 levels are increased following DNA damage in a p53-dependent manner.

p53 plays a central role in the cellular response to stressful stimuli, including DNA damage, aberrant growth signals, and hypoxia. Upon activation, it binds to a specific DNA binding motif and functions to transcriptionally activate or repress different groups of genes. The biologic outcome of these events can lead to cell-cycle arrest, DNA repair, or apoptosis. While many downstream targets of p53 have been identified, the factors that determine which of these outcomes will occur in an individual cell are less clear. In this study, we show that caspase 10, an initiator caspase, is induced in response to DNA damaging chemotherapeutic agents in a p53-dependent manner. Following treatment with etoposide or adriamycin, induction of caspase 10 occurred at both the mRNA and protein levels. In contrast, DNA damage did not affect levels of caspase 8, another initiator caspase with significant structural and functional homology to caspase 10. By chromatin immunoprecipitation assay, p53 bound in vivo to multiple p53-specific binding sites located within the caspase 10 gene locus, suggesting that caspase 10 is a direct transcriptional target of p53. Upregulation of caspase 10 may represent one factor that determines how p53 activation leads to cellular apoptosis following DNA damage.

Adenoviridae↗

PubMed1999

Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II.

Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor independent missense mutations in Caspase 10. These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL. These results provide evidence that inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Caspase-mediated Cleavage of Insulin Receptor Substrate.

Apoptosis is an important mechanism for maintaining tissue homeostasis. The efficient induction and execution of apoptosis are essential for cell clearance in specific developmental situations. Insulin-like growth factor (IGF)-I is a survival factor for epithelial cells in the mammary gland, and its withdrawal or inhibition leads to apoptosis. In this paper we describe a novel mechanism that may lead to suppression of an IGF-I-mediated signaling pathway through cleavage of insulin receptor substrate (IRS). During the process of forced weaning, when mammary epithelial cells rapidly enter apoptosis in vivo, IRS-1 and IRS-2 disappear. We have used cultured mammary epithelial cells to demonstrate that IRS removal can be mediated through the action of caspase 10. Caspase 10 activation and IRS-1 cleavage are regulated by a MKK1-signaling pathway but not by a phosphatidylinositol-3 kinase pathway nor by the extracellular proapoptotic ligands FasL, tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), or transforming growth factor-beta3. In addition we show that the loss of IRS-1 after MKK1 inhibition prevents IGF-mediated phosphorylation of FKHRL1.

Animals↗

PubMed2005

Licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes.

The accumulation of hydrophobic bile acids results in cholestatic liver injury by increasing oxidative stress, mitochondrial dysfunction, and activation of cell signaling pathways. Licorice root and its constituents have been utilized as antihepatotoxic agents. The purpose of this study was to evaluate the potential modulation by a primary component of licorice root, glycyrrhizin (GL), and its metabolite, 18beta-glycyrrhetinic acid (GA), in a hepatocyte model of cholestatic liver injury. Preincubation of fresh rat hepatocyte suspensions with GL or GA reduced glycochenodeoxycholic acid (GCDC)-dependent reactive oxygen species generation, with GA more potent than GL. Interestingly, GL and GA had opposing effects toward GCDC-induced cytotoxicity; GA prevented both necrosis and apoptosis, whereas GL enhanced apoptosis. GCDC promoted activation of caspase 10, caspase 3, and PARP; all were inhibited by GA but not GL. Induction of apoptosis by GCDC was also associated with activation of JNK, which was prevented by GA. Activation of caspase 9 and dissipation of mitochondrial membrane potential were prevented by GA but not GL. In liver mitochondrial studies, GL and GA were both potent inhibitors of the mitochondrial permeability transition, reactive oxygen species generation, and cytochrome c release at submicromolar concentrations. Results from this study suggest that GL exhibits pro-apoptotic properties, whereas GA is a potent inhibitor of bile acid-induced apoptosis and necrosis in a manner consistent with its antioxidative effect.

Animals↗

PubMed2005

The human cytomegalovirus-encoded chemokine receptor US28 induces caspase-dependent apoptosis.

Viral subversion of apoptosis regulation plays an important role in the outcome of host/virus interactions. Although human cytomegalovirus (HCMV) encodes several immediate early (IE) antiapoptotic proteins (IE1, IE2, vMIA and vICA), no proapoptotic HCMV protein has yet been identified. Here we show that US28, a functional IE HCMV-encoded chemokine receptor, which may be involved in both viral dissemination and immune evasion, constitutively induces apoptosis in several cell types. In contrast, none of nine human cellular chemokine receptors, belonging to three different subfamilies, induced any significant level of apoptosis. US28-induced cell death involves caspase 10 and caspase 8 activation, but does not depend on the engagement of cell-surface death receptors of the tumour necrosis factor receptor/CD95 family. US28 cell-death induction is prevented by coexpression of C-FLIP, a protein that inhibits Fas-associated death domain protein (FADD)-mediated activation of caspase 10 and caspase 8, and by coexpression of the HCMV antiapoptotic protein IE1. The use of US28 mutants indicated that the DRY sequence of its third transmenbrane domain, required for constitutive G-protein signalling, and the US28 intracellular terminal domain required for constitutive US28 endocytosis, are each partially required for cell-death induction. Thus, in HCMV-infected cells, US28 may function either as a chemokine receptor, a phospholipase C activator, or a proapoptotic factor, depending on expression levels of HCMV and/or cellular antiapoptotic proteins.

Apoptosis↗

PubMed2005

Mechanism of anti-apoptotic action of dipfluzine on neuronal damage of the rat hippocampal CA1 region subjected to transient forebrain ischemia.

AIM: To explore the relations between anti-apoptotic role of dipfluzine (DIP) and the death signaling transduction pathway initiated by CD95 molecules, and the transcription factor involved in the transcription regulation of CD95 molecules in the hippocampal CA1 region after transient forebrain ischemia. METHODS: The rat forebrain transient ischemia model was established through 15 min ischemia followed by 3 days reperfusion by using the four-vessel method. The rats were divided randomly into five groups: sham control group, ischemia/reperfusion (I/R) group, DIP treated groups (20, 40 and 80 mg x kg(-1) body weight, ig, separately). Western blotting and RT-PCR were performed to detect the expression changes of Fas, FasL, caspase 10 p20, caspase 8, I-kappaB-alpha, and p-I-kappaB-alpha molecules in protein and mRNA levels, separately, and immunohistochemistry for molecular localization of Fas and FasL in rat hippocampus. RESULTS: The expression of Fas, FasL, and caspase 10 p20 in protein and mRNA levels increased after I/R, which was inhibited significantly after treatment with 20 and 40 mg x kg(-1) of DIP (P < 0.01). In 80 mg x kg(-1) of DIP group, the expression of Fas and FasL protein was not significantly different from that of I/R group (P > 0.05). The expression of caspase 8 and I-kappaB-alpha showed no significant differences in all groups (P > 0.05), and no gene expression was observed for p-I-kappaB-alpha protein in the study. DIP significantly affected molecular distribution of Fas and FasL protein in CA1 subregion of hippocampus. CONCLUSION: DIP inhibits the death signaling transduction pathway initiated by CD95 molecules in rat hippocampal CA1 subregion, and NF-kappaB transcription factor may not be involved in the transcription regulation of CD95 molecules after transient forebrain ischemia.

Animals↗

PubMed2003

Differential expression of intracellular apoptotic signaling molecules in tumor and tumor-infiltrating lymphocytes during development of invasion and/or metastasis of gastric carcinoma.

The presence and functional status of intracellular expression of caspase 8, caspase 10, cFLIP, caspase 3, survivin, and NF-kappaB was investigated in permeabilized tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma (N = 20) from primary locus, metastatic gastric carcinoma (N = 22) from malignant ascites, and benign gastric mucosa (N = 20) for the control. The quantitative analysis was based on the percentage of positive cells by a flow cytometry. The results showed that the six intracellular molecules were constitutively expressed in primary and metastatic carcinomas as well as normal epithelium in nearly all the patients. In particular, metastatic carcinoma revealed to significantly overexpress these molecules. In the analysis of TIL, the expression of these six molecules could usually be observed in carcinoma and normal epithelium. There was aberrant expression of these molecules in immune TIL within metastatic carcinoma nests. Taken together, the results showed the significantly different expression of the signaling molecules in both tumor and TIL between primary and metastatic carcinoma nests. Increased expression of cFLIP, survivin, and NF-kappaB in carcinoma might play an important role in hindering an intracellular apoptotic process, followed by accelerating the cancer invasion and/or metastasis.

Adult↗

PubMed2005

Caspase 8/10 are not mediating apoptosis in neuroblastoma cells treated with CDK inhibitory drugs.

Olomoucine and Roscovitine are pharmacological inhibitors of cyclin-dependent kinases (CDK) displaying a promising profile as anticancer agents. Both compounds are effective inductors of apoptosis in a human neuroblastoma cell line, SH-SY5Y. The characterization of this process had suggested the involvement of an extrinsic pathway [Ribas, J., Boix, J., 2004. Cell differentiation, Caspase inhibition, and macromolecular synthesis blockage, but not Bcl-2 or Bcl-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two CDK inhibitory drugs. Exp. Cell Res. 295 9-24.], which depends on either Caspase 8 or Caspase 10 activation. However, neither Caspase 8 nor Caspase 10 is expressed in SH-SY5Y cells because of gene silencing. Upon Olomoucine or Roscovitine treatment, no re-expression of Caspase 8 or Caspase 10 was found. Therefore, in SH-SY5Y cells, this type of drugs is not triggering a canonical, Caspase 8/10-mediated, extrinsic apoptotic pathway.

Amino Acid Chloromethyl Ketones↗

PubMed2002

Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas.

Caspase 10 (Mch4/FLICE2) is a caspase homologous to caspase 8. A recent report described that inherited CASP10 gene mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome (ALPS). In this study, to explore the possibility that mutation of this gene might be involved in the development of non-Hodgkin lymphoma (NHL), we have analyzed the entire coding region and all splice sites of the CASP10 gene for the detection of somatic mutations in 117 human NHLs. Overall, 17 NHLs (14.5%) were found to have CASP10 mutations, which were identified in the coding regions of the prodomain (n = 3), the p17 large protease subunit (n = 11), and the p12 small protease subunit (n = 3). We expressed the tumor-derived caspase 10 mutants in 293 cells and found that apoptosis was suppressed. These data suggest that the inactivating mutations of the CASP10 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human NHLs.

Alleles↗

PubMed2005

Caspase 8 is absent or low in many ex vivo gliomas.

BACKGROUND: Better treatments are required urgently for patients with malignant glioma, which currently is incurable. Death ligands, such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), may offer promise for the treatment high-grade glioma if such ligands induce apoptotic signaling in vivo in glioma cells. Caspase 8 is required for death ligand signaling, and its levels may influence the sensitivity of glioma cells to death ligands. It also may act as a tumor suppressor protein. The authors analyzed caspase 8 expression levels in ex vivo glioma specimens and explored potential mechanisms of its regulation. METHODS: Eleven glioblastomas, 5 anaplastic astrocytomas, and 3 low-grade astrocytomas were studied. The levels of caspase 8, caspase 10, cellular FLICE inhibitory protein (c-FLIP), and signal transducer and activator of transcription (STAT)-1 were assayed using quantitative immunoblotting. Caspase 8 mRNA was measured by Northern blot analysis. The methylation status of the caspase 8 gene was determined by bisulfate modification of genomic DNA, cloning, and sequencing. Statistical analyses were performed using nonparametric (Spearman) correlations. RESULTS: Some ex vivo glioma samples lacked detectable caspase 8, with many expressing barely detectable levels. No tumors expressed significant amounts of caspase 10 or c-FLIP. A strong association was found between caspase 8 mRNA and protein levels. Neither expression of the transcription factor STAT-1 nor caspase 8 gene methylation correlated with caspase 8 levels. CONCLUSIONS: The absence of caspase 8 protein in many resected glioma samples implied that many patients with glioma may not benefit from death ligand-based treatments, unless caspase 8 (or caspase 10) protein expression can be elevated. Demethylating agents are unlikely to boost caspase 8 levels in glioma cells, but treatments that increase caspase 8 mRNA levels may up-regulate expression of the protein.

Astrocytoma↗

PubMed2004

Induction of apoptosis by X-linked ectodermal dysplasia receptor via a caspase 8-dependent mechanism.

X-linked ectodermal dysplasia receptor (XEDAR) is a recently isolated member of the tumor necrosis factor receptor family that is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2). In this report, we demonstrate that although XEDAR lacks a death domain, it nevertheless induces apoptosis in an EDA-A2-dependent fashion. The apoptosis-inducing ability of XEDAR is dependent on the activation of caspase 8 and can be blocked by its genetic and pharmacological inhibitors. Although XEDAR-induced apoptosis can be blocked by dominant-negative Fas-associated death domain (FADD) protein and FADD small interfering RNA, XEDAR does not directly bind to FADD, tumor necrosis factor receptor-associated death domain (TRADD) protein, or RIP1. Instead, XEDAR signaling leads to the formation of a secondary complex containing FADD, caspase 8, and caspase 10, which results in caspase activation. Thus, XEDAR belongs to a novel class of death receptors that lack a discernible death domain but are capable of activating apoptosis in a caspase 8- and FADD-dependent fashion. XEDAR may represent an early stage in the evolution of death receptors prior to the emergence of the death domain and may play a role in the induction of apoptosis during embryonic development and adult life.

Apoptosis↗

PubMed1998

Ultraviolet-irradiation-induced apoptosis is mediated via ligand independent activation of tumor necrosis factor receptor 1.

Ultraviolet (UV)-irradiation has been shown to induce jun N-terminal kinase activity via aggregation-mediated activation of tumor necrosis factor receptor 1 (TNFR1) but the role of TNFR1 in mediating UV-induced apoptosis has not been explored. Using p53-null cells, we demonstrate that UV-stimulated ligand independent activation of TNFR1 plays a major role in mediating the apoptotic effects of UV-irradiation. UV-irradiation and TNF alpha acted in a synergistic manner to induce apoptosis. UV-irradiation stimulated the aggregation-mediated activation of TNFR1 which was coupled with activation of caspase 8, the most proximal caspase in TNF alpha signaling pathway. CrmA and the dominant negative versions of FADD, caspase 8 and caspase 10, that block the apoptotic axis of TNFR1 at different levels, also independently inhibited the UV-induced apoptosis. The engagement of the membrane initiated events was specific for UV-irradiation since neither CrmA nor the dominant negative FADD, caspase 8 or caspase 10 blocked the ionizing radiation-induced apoptosis. Cisplatin and melphalan, the UV-mimetic agents known to elicit UV-type DNA damage, also induced apoptosis but differed from UV in that both of the former agents engaged the caspase cascade at a level distal to FADD. Consistent with these findings cisplatin also did not stimulate TNFR1 aggregation. Together these results indicate that DNA damage per se was not sufficient to activate the membrane TNFR1. Based on our results we propose that the plasma membrane initiated events play a predominant role in mediating UV-irradiation-induced apoptosis and that UV-irradiation appears to engage the apoptotic axis of TNFR1 and perhaps those of other membrane death receptors to transduce its apoptotic signals.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Alterations of Fas-pathway genes associated with nodal metastasis in non-small cell lung cancer.

Many types of cancer cells are resistant to Fas-mediated apoptosis by several mechanisms, including the mutations of the genes involved in Fas-mediated apoptosis. In this study, to explore the possibility that the mutations of the genes involved in the proximal pathway of Fas-mediated apoptosis (Fas, FADD, caspase 8 and caspase 10) are involved in cancer metastasis, we have analysed somatic mutation and deletion of these genes in 80 non-small cell lung cancers (NSCLCs) with (n=43) and without (n=37) metastasis to the regional lymph nodes. We found 12 mutations (four Fas, four FADD, and four caspase 10 mutations) in 11 of 80 NSCLCs (13.8%). Interestingly, of these mutations, most mutations (10 out of 12) were detected in the NSCLCs with metastasis, and the frequency in the metastasis lesions (23%) was higher than that in the primary lesions of the NSCLCs without metastasis (5.4%). Furthermore, transfection study revealed that the tumor-derived mutants have decreased apoptosis inductions compared to the wild types. These data suggest that the inactivating mutations of the genes in the proximal pathway of Fas-mediated apoptosis may lead to a decreased cancer cell death and play a role in the metastasis of NSCLC.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variant.

Dysregulation of apoptosis plays a crucial role in carcinogenesis. As part of death receptor- and mitochondrion-mediated apoptosis, the homologues caspases 10 and 8 may act as low-penetrance breast cancer (BC) susceptibility genes. In death receptor-mediated apoptosis, engagement of death receptors by their ligands involves the assembly of the death-inducing signalling complex (DISC). In mitochondrion-mediated apoptosis, the release of cytochrome c into the cytosol results in apoptosome formation. Recruitment of both caspases 10 and 8 (CASP10 and CASP8, respectively) to DISC and apoptosome leads to their activation by dimerization. We investigated the influence of the coding CASP10 variant V410I (G1228A) by performing a case-control study - using 511 familial BC cases and 547 control subjects - on BC risk and revealed a significant association of V410I with a reduced risk (OR = 0.62, 95% CI = 0.43-0.88, P = 0.0076) related to the number of variant alleles (P(trend) = 0.0039). As CASP10 and CASP8 functionally co-operate during apoptosis, we analysed the mutual effect of both CASP10 V410I and CASP8 D302H, resulting in a significant association between the number of the variant alleles I410 and H302 and a highly decreased familial BC risk (OR = 0.35, P(trend) = 0.007), pointing to the interaction between the CASP10 and CASP8 polymorphisms in breast carcinogenesis.

Adult↗

PubMed2000

Activation of the NF-kappaB pathway by caspase 8 and its homologs.

Caspase 8 is the most proximal caspase in the caspase cascade and has been known for its role in the mediation of cell death by various death receptors belonging to the TNFR family. We have discovered that Caspase 8 can activate the NF-kappaB pathway independent of its activity as a pro-apoptotic protease. This property is localized to its N-terminal prodomain, which contains two homologous death effector domains (DEDs). Caspase 10 and MRIT, two DEDs-containing homologs of Caspase 8, can similarly activate the NF-kappaB pathway. Dominant-negative mutants of the Caspase 8 prodomain can block NF-kappaB induced by Caspase 8, FADD and several death receptors belonging to the TNFR family. Caspase 8 can interact with multiple proteins known to be involved in the activation of the NF-kappaB pathway, including the serine-threonine kinases RIP, NIK, IKK1 and IKK2. Thus, DEDs-containing caspases and caspase homolog(s) may have functions beyond their known role in the mediation of cell death. Oncogene (2000) 19, 4451 - 4460.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Support for an infection-induced apoptotic pathway in human fetal membranes.

OBJECTIVE: Lipopolysaccharide and tumor necrosis factor alpha levels are both elevated in the amniotic fluid of women during infection-associated preterm labor and premature rupture of fetal membranes. Our laboratory has shown that apoptosis is associated with premature rupture of fetal membranes but is not associated with preterm labor. The exact pathway that leads to apoptosis-mediated premature rupture of fetal membranes is still unclear. Because infection and increased inflammatory cytokine response are associated with the majority of cases of premature rupture of fetal membranes, we examined the roles of bacterial lipopolysaccharide and tumor necrosis factor alpha in inducing the proapoptotic caspase pathway in fetal membranes. STUDY DESIGN: Amniochorionic membranes collected from women undergoing elective repeat cesarean delivery at term were placed in an organ explant system. At the end of a 48-hour incubation period, membranes were stimulated with lipopolysaccharide (50 ng/mL) and recombinant tumor necrosis factor (50 ng/mL). Total ribonucleic acid extracted from these samples was subjected to reverse transcription and two separate sets of multiple polymerase chain reaction. One set studied the expression of Fas, Fas ligand, caspase 8, Fas-associated death domain, and tumor necrosis factor receptor-associated death domain genes and the second set studied the expression of caspase 2, 4, 6, 7, and 10. Caspase 2, 3, and 9 expression was also studied by reverse transcriptase-polymerase chain reaction. RESULTS: Multiple polymerase chain reactions and reverse transcriptase-polymerase chain reactions documented the induction of Fas and caspase 2, 3, 7, 8, and 9 genes in amniochorion after lipopolysaccharide and tumor necrosis factor stimulation compared with the nonstimulated controls. Neither lipopolysaccharide nor tumor necrosis factor induced Fas ligand expression in human fetal membranes. Caspase 3, 4, and 6, Fas-associated death domain, and tumor necrosis factor receptor-associated death domain expressions were constitutive in all the tissues tested; however, tumor necrosis factor receptor-associated death domain expression appeared stronger in tumor necrosis factor-stimulated tissues. CONCLUSION: The presence of the signal docking proteins tumor necrosis factor receptor-associated death domain and Fas-associated death domain and the induction of caspase cascade initiators (caspase 2, 8, and 10) and effector caspases (caspase 3, 6, 7, and 9) by lipopolysaccharide and tumor necrosis factor suggest that tumor necrosis factor-tumor necrosis factor receptor-mediated apoptosis may occur in the human fetal membrane.

Adaptor Proteins, Signal Transducing↗

PubMed2003

A caspaselike activity is triggered by LPS and is required for survival of human dendritic cells.

Bacterial endotoxin (lipopolysaccharide [LPS]) is a potent inducer of human dendritic cell (DC) maturation and survival. Here we show that immature DCs exposed to LPS trigger an early and sustained caspase-like activity, which can be blocked by zVAD (z-Val-Ala-Asp), in the absence of detectable caspase 8 and caspase 10 activation, or poly(ADP-ribose) polymerase (PARP)-cleaving activity. Preventing LPS-induced caspase-like activation in DC results in massive cell death. Importantly, triggering of the caspase-like activity is required for LPS-induced activation of extracellular signal-regulated kinases (ERKs) and for LPS-induced up-regulation of cFLIP (Fas-associating protein with death domain-like interleukin-1 beta-converting enzyme [FLICE]-like inhibitory protein). Therefore, a caspase-dependent pathway initiated by LPS controls survival of human DCs.

Blotting, Western↗

PubMed1999

Autoimmune lymphoproliferative syndrome, a disorder of apoptosis.

Autoimmune Lymphoproliferative Syndrome (ALPS) is a recently recognized disease in which a genetic defect in programmed cell death, or apoptosis, leads to breakdown of lymphocyte homeostasis and normal immunologic tolerance. Some authors have referred to ALPS as Canale-Smith syndrome or lymphoproliferative syndrome with autoimmunity. Patients with ALPS have chronic enlargement of the spleen and lymph nodes, various manifestations of autoimmunity, and elevation of a normally rare population of "double negative T cells" (DNTs), T lymphocytes bearing alpha beta T cell receptors and expressing neither cluster differentiation (CD)4 nor CD8 surface antigens. When lymphocytes from patients with ALPS are cultured in vitro, they are resistant to apoptosis as compared to cells from healthy controls. Most patients with ALPS have mutations in a gene now named TNFRSF6 (tumor necrosis factor receptor gene superfamily member 6). This gene, previously known as apoptosis antigen 1 (APT1), encodes the cell surface receptor for the major apoptosis pathway in mature lymphocytes; this receptor has also had many names, including Fas (to be used here), CD95, and APO-1. ALPS is subdivided into: 1) Type Ia, ALPS with mutant Fas; 2) Type Ib, lymphadenopathy and mutation in the ligand for Fas in one patient with systemic lupus erythematosus; 3) Type II, ALPS with mutant caspase 10; and 4) Type III, ALPS as yet without any defined genetic cause.

Apoptosis↗