Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome

Zhu, Shuyu; Hsu, Amy P.; Vacek, Marla M.; Zheng, Lixin; Schäffer, Alejandro A.; Dale, Janet K.; Davis, Joie; Fischer, Roxanne; Straus, Stephen E.; Boruchov, Donna; Saulsbury, Frank T.; Puck, Jennifer M.

doi:10.1007/s00439-006-0138-9

Cited by 67 publications

(72 citation statements)

References 30 publications

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“…92 Recently, caspase-10, along with caspase-8, was shown to be essential for mediating NF-kB-dependent inflammatory responses in antiviral signalling. 93 Missense and inactivating mutations in casp10 gene have been reported to be associated with some cases of the autoimmune lymphoproliferative syndrome II (ALPS II), 94 non-Hodgkin lymphoma 95 and gastric cancer, 96 however it is unclear whether these mutations directly contribute to the disease phenotype.…”

Section: The Apoptotic Caspases S Kumarmentioning

confidence: 99%

Caspase function in programmed cell death

2006

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The first proapoptotic caspase, CED-3, was cloned from Caenorhabditis elegans in 1993 and shown to be essential for the developmental death of all somatic cells. Following the discovery of CED-3, caspases have been cloned from several vertebrate and invertebrate species. As reviewed in other articles in this issue of Cell Death and Differentiation, many caspases function in nonapoptotic pathways. However, as is clear from the worm studies, the evolutionarily conserved role of caspases is to execute programmed cell death. In this article, I will specifically focus on caspases that function primarily in cell death execution. In particular, the physiological function of caspases in apoptosis is discussed using examples from the worm, fly and mammals.

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Section: The Apoptotic Caspases S Kumarmentioning

confidence: 99%

Caspase function in programmed cell death

2006

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“…32 In humans, genetic alterations in caspase-10 may be causative or protective in type II autoimmune lymphoproliferative syndrome, most likely due to its role in the initiation of the extrinsic apoptotic pathway. 33 Furthermore, caspase-10 has been implicated in the activation of NF-kB-dependent prosurvival signaling pathways, by a mechanism that may not require its catalytic domain. 34 Caspase-11 was first described as an obligate activator of caspase-1.…”

Section: Vital Functions Of Mammalian Caspasesmentioning

confidence: 99%

No death without life: vital functions of apoptotic effectors

et al. 2008

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As a result of the genetic experiments performed in Caenorhabditis elegans, it has been tacitly assumed that the core proteins of the 'apoptotic machinery' (CED-3, -4, -9 and EGL-1) would be solely involved in cell death regulation/execution and would not exert any functions outside of the cell death realm. However, multiple studies indicate that the mammalian orthologs of these C. elegans proteins (i.e. caspases, Apaf-1 and multidomain proteins of the Bcl-2 family) participate in cell death-unrelated processes. Similarly, loss-of-function mutations of ced-4 compromise the mitotic arrest of DNA-damaged germline cells from adult nematodes, even in a context in which the apoptotic machinery is inoperative (for instance due to mutations of egl-1 or ced-3). Moreover, EGL-1 is required for the activation of autophagy in starved nematodes. Finally, the depletion of caspaseindependent death effectors, such as apoptosis-inducing factor (AIF) and endonuclease G, provokes cell death-independent consequences, both in mammals and in yeast (Saccharomyces cerevisiae). These results corroborate the conjecture that any kind of protein that has previously been specifically implicated in apoptosis might have a phylogenetically conserved apoptosisunrelated function, most likely as part of an adaptive response to cellular stress.

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“…29 A handful of patients have germline deleterious mutations in genes encoding FASL or CASP10. 30,31 …”

Section: Geneticsmentioning

confidence: 99%

How I treat autoimmune lymphoproliferative syndrome

Rao

Oliveira²

2011

Blood

166

153

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Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis, permitting accumulation of lymphoid mass and persistence of autoreactive cells that often manifest in childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Cytopenias in these patients can be the result of splenic sequestration as well as autoimmune complications manifesting as autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. More than 300 families with hereditary ALPS have now been described; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years by our colleagues and ourselves. Some of these patients with FAS mutations affecting the intracellular portion of the FAS protein also have an increased risk of B-cell lymphoma. The best approaches to diagnosis, followup, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented. This trial was registered at www.clinicaltrial.gov as #NCT00001350. (Blood. 2011;118(22): 5741-5751) IntroductionAutoimmunity results from failure of self-tolerance, which can be further divided into central and peripheral tolerance. Central tolerance is fostered by apoptosis through elimination of autoreactive lymphocytes in generative lymphoid organs (the bone marrow and thymus), whereas mechanisms of peripheral tolerance include anergy, deletion by apoptosis, and suppression by regulatory T cells to avoid autoimmunity and tissue damage. 1 Apoptosis, the intrinsic program of cell death, is triggered by receptor-ligand interactions at the cell surface (the extrinsic pathway) or by the activation of mitochondrial proteins (the intrinsic pathway), leading to processing and activation of caspases and their downstream targets. Lymphocyte apoptosis mediated by the cell surface receptor FAS plays a pivotal role in lymphocyte homeostasis. FAS (also termed CD95/APO1) is a member of the tumor necrosis factor receptor superfamily of proteins that directly trigger apoptosis to maintain lymphocyte homeostasis and peripheral immune tolerance and prevent autoimmunity. 2,3 It is a membrane-bound molecule that is highly expressed, not only on activated B and T lymphocytes but also present in other cells, such as hepatocytes. FAS is present on the cell surface as a preformed trimer. 4 Its binding with FAS ligand leads to conformational changes on the intracellular portion of FAS protein triggering rapid recruitment of the death domain of the adaptor protein FADD (Fas-associated death domain) to the homologous death domain in the cytoplasmic tail of FAS. This is followed by the recruitment of procaspases 8 or 10 through the interaction of their death-effecter domains with the amino termini of FADD. The resulting Fas/FADD/caspase complex is termed the death-inducing signaling complex that incites a further cascade of caspase activation culminati...

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Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome

Cited by 67 publications

References 30 publications

Caspase function in programmed cell death

Caspase function in programmed cell death

No death without life: vital functions of apoptotic effectors

How I treat autoimmune lymphoproliferative syndrome

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