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Caspase Function
Published by Anonymous on 2007/9/29 (1935 reads)
1: Cell Death Differ. 2007 Jan;14(1):32-43. Epub 2006 Nov 3.


Caspase function in programmed cell death.

Kumar S.

Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia. sharad.kumar@imvs.sa.gov.au

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.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 17082813 [PubMed - indexed for MEDLINE]

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2: Crit Rev Immunol. 2006;26(2):133-48.


Caspase function and the immune system.

Sehra S, Dent AL.

Department of Microbiology and Immunology and The Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Caspases are key effector components of apoptosis, the process of programmed cell death. However, a large body of recent work has shown that caspase activity is necessary for several nonapoptotic cellular functions, such as proliferation, differentiation, survival, and the regulation of cytokine expression. In this review, we concentrate on the nonapoptotic functions of caspases and, in particular, on nonapoptotic roles of caspases in the immune system. Because of the involvement of caspases in promoting cell death, as well as cell proliferation and other nonapoptotic functions, studies involving the inhibition of caspases in vivo must be interpreted with caution.

Publication Types:
Review

PMID: 16700650 [PubMed - indexed for MEDLINE]

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3: Ann Clin Biochem. 2005 Nov;42(Pt 6):415-31.


Caspase and calpain function in cell death: bridging the gap between apoptosis and necrosis.

Harwood SM, Yaqoob MM, Allen DA.

Centre for Experimental Medicine, Nephrology and Critical Care, Renal Research Laboratories, William Harvey Research Institute, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK. s.m.harwood@qmul.ac.uk

Calpain and caspase are families of cysteine proteases that have important roles in the initiation, regulation and execution of cell death. The function of both groups of proteases in the progression of apoptotic and necrotic pathways is presented here in the context of a concise overview of regulated cell death. Many of the morphological differences between apoptotic and necrotic processes are thought to be as a consequence of the action of cysteine proteases. Recent studies suggest that caspase and calpain cascades are tightly interrelated and an appreciation of how these proteases cross-talk should enable a greater understanding of how the boundaries between apoptotic and necrotic cell death have become blurred. Furthermore, an assessment of the contribution that caspase and calpain make to human physiology and pathology is provided, with a description of how these proteases can be detected and quantified. Lastly, an evaluation is made of how caspase and calpain activation might be exploited diagnostically.

Publication Types:
Review

PMID: 16259792 [PubMed - indexed for MEDLINE]

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4: Biochem Biophys Res Commun. 2005 Jun 10;331(3):859-67.


Caspase-2 function in response to DNA damage.

Zhivotovsky B, Orrenius S.

Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden. Boris.Zhivotovsky@imm.ki.se

Caspase-2 is one of the best conserved caspases across species. This enzyme is unique among caspases in that it has features of both initiator and effector caspases. Caspase-2 appears to be necessary for the onset of apoptosis triggered by several insults, including DNA damage, administration of TNF, and different pathogens and viruses. In several experimental systems, a link has been shown between the p53 family proteins and caspase-2 activation leading to cell death. In this review, current knowledge concerning the structure of this protease and its function in cell physiology and cell death, particularly cell death triggered by DNA damage, is summarized and discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15865942 [PubMed - indexed for MEDLINE]

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5: Curr Drug Targets CNS Neurol Disord. 2005 Feb;4(1):51-61.


Caspase function in neuronal death: delineation of the role of caspases in ischemia.

Prunell GF, Arboleda VA, Troy CM.

Department of Pathology, Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, 630 W 168 ST, New York, NY 10032, USA.

Cerebral ischemia is one of the major causes of morbidity and mortality in the Western world. Despite extensive research, adequate therapies are still elusive. Neuronal degeneration and death are hallmarks of stroke/ischemia. Understanding how the death machinery executes neuronal death in ischemia will provide therapeutic targets. Key to the death machinery are caspases: the family of cell death proteases. While much data has been published regarding caspase involvement in models of ischemia, the pathways have not been thoroughly defined. The specification of the caspases critical for death has been hampered by the use of non-specific reagents. Thus many conclusions about specificity are unwarranted. In this review we discuss how caspases can be measured and review the existing knowledge of the roles of specific caspases in ischemia. We also discuss approaches to determining the molecules that execute ischemic death.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 15723613 [PubMed - indexed for MEDLINE]

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6: Drug Resist Updat. 2004 Feb;7(1):11-7.


Subcellular targeting regulates the function of caspase-activated protein kinases in apoptosis.

Jakobi R.

Department of Biochemistry, The University of Health Sciences, 1750 Independence Avenue, Kansas City, MO 64106, USA. rjakobi@uhs.edu

Subcellular localization and targeting of proteins play important roles in signal transduction pathways that regulate cell survival and programmed cell death. The regulation of cell survival and cell death requires translocation of many anti- and pro-apoptotic signaling molecules from one subcellular compartment to another. In many cases translocation is triggered by caspase cleavage. Caspase cleavage removes the regulatory domains of the protein kinases MEKK1, Mst-1 and PAK-2 resulting in activation and in relocalization of the catalytic fragments. Caspase-activated MEKK1 translocates from a particulate compartment to the cytosol; caspase-activated Mst-1 and PAK-2 translocate from the cytoplasm to the nucleus. Caspase activation of these protein kinases induces a cell death response. Relocalization of the catalytic fragments to a pro-apoptotic location appears to be required to induce cell death. It is suggested that translocation to a pro-apoptotic location results in phosphorylation of pro-apoptotic substrates. Therefore, these protein kinases could represent novel targets for cancer therapy. Compounds that stimulate cleavage of MEKK1, Mst-1 and PAK-2 or compounds that cause translocation to a pro-apoptotic location could be used to induce cell death of cancer cells.

Publication Types:
Review

PMID: 15072767 [PubMed - indexed for MEDLINE]

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7: Immunol Rev. 2004 Feb;197:129-46.


Modulation and function of caspase pathways in B lymphocytes.

Graves JD, Craxton A, Clark EA.

Department of Immunology, University of Washington, Seattle, WA 98195, USA.

During their development, B-lineage cells are selected to mature, to die, to divide, or to survive and wait, ready to respond to external signals. The homeostatic balance between growth, death, and survival is mediated by signaling pathways through the B-cell antigen receptor (BCR) complex, cytokine and chemokine receptors or cell-cell coreceptor interactions. The BCR complex is a master regulator essential at key checkpoints during development. These checkpoints involve various processes, including negative selection (deletion), anergy, receptor editing, and positive selection. Without BCRs or downstream BCR-signaling components, B-lineage cells arrest during development. Removal of BCRs from mature B cells leads to their death. Here, we discuss signaling pathways in B cells that activate members of the caspase family of cysteine proteases. In some B-cell subsets, BCR signaling activates caspases, which in turn induce a program leading to cell death. However, in other contexts, caspases are involved in the proliferation of B cells. The outcome depends in part on the presence or absence of modifiers that affect signaling thresholds and on which caspases are activated. These mechanisms allow the coordinated regulation of proliferation and apoptosis that is essential for lymphoid homeostasis.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 14962192 [PubMed - indexed for MEDLINE]

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8: Tanpakushitsu Kakusan Koso. 2001 Mar;46(3):233-9.


[Structure and function of the CAD domains of caspase-activated DNase(CAD) and inhibitor of CAD]

[Article in Japanese]

Otomo T, Yamazaki T, Uegaki K, Sakahira H, Nagata S.

Publication Types:
Review

PMID: 11244720 [PubMed - indexed for MEDLINE]

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9: Exp Cell Res. 2000 Apr 10;256(1):67-73.


Divinations and surprises: genetic analysis of caspase function in mice.

Zheng TS, Flavell RA.

Biogen, Inc., Department of Inflammation, Immunology and Cell Biology, 14 Cambridge Center, Cambridge, Massachusetts 02142, USA. timothy_zheng@biogen.com

Caspases are critical mediators of apoptosis, the principle mechanism by which extra and harmful cells are eliminated to ensure proper development and maintain cellular homeostasis in all multicellular organisms. While compelling evidence suggests that the activation of these otherwise latent intracellular proteases is required for the execution of most, if not all apoptosis in mammals, the presence of more than a dozen caspases presents a major challenge to our understanding of the precise function of individual caspases in vivo. Using a genetic approach, several groups have generated transgenic mice deficient in various caspases so as to investigate their physiological functions. In this review, we will discuss what these studies have revealed about the role of individual caspase in development, apoptosis, and inflammation, with a particular focus on the predictable phenotypes versus the surprises based on in vitro results, as well as the implications of these findings. Copyright 2000 Academic Press.

Publication Types:
Review

PMID: 10739653 [PubMed - indexed for MEDLINE]

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10: Cell Death Differ. 1999 Nov;6(11):1028-42.


Caspase structure, proteolytic substrates, and function during apoptotic cell death.

Nicholson DW.

Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada & Co., PO Box 1005, Pointe Claire-Dorval, Quebec, Canada, H9R 4P8. donald_nicholson@merck.com

Caspases play an essential role during apoptotic cell death. These enzymes define a new class of cysteine proteases and comprise a multi-gene family with more than a dozen distinct mammalian family members. The discrete and highly limited subset of cellular polypeptides that are cleaved by these proteases is sufficient to account for the majority of cellular and morphological events that occur during cell death. In some cases, caspases also play a contributory role in escalating the propensity for apoptosis, and in doing so may exacerbate disease pathogenesis.

Publication Types:
Review

PMID: 10578171 [PubMed - indexed for MEDLINE]
 

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