Apoptotic Threshold Is Lowered by P53 Transactivation of Caspase-6
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HAC-1, a Drosophila Homolog of APAF-1 and CED-4, Functions in Developmental and Radiation-Induced Apoptosis
Molecular Cell, Vol. 4, 745±755, November, 1999, Copyright 1999 by Cell Press HAC-1, a Drosophila Homolog of APAF-1 and CED-4, Functions in Developmental and Radiation-Induced Apoptosis Lei Zhou, Zhiwei Song,² Jan Tittel,² generation of a large (p20) and small (p10) subunit. Cas- and Hermann Steller* pases can be activated through cleavage by active ªiniti- Howard Hughes Medical Institute atorº caspases in a caspase cascade (Li et al., 1997), Department of Biology and by autoproteolysis following aggregation of two or Massachusetts Institute of Technology more zymogen molecules (MacCorkle et al., 1998; Muzio Cambridge, Massachusetts 02139 et al., 1998; Yang et al., 1998). Upon activation of ªexecu- tionerº caspases, a wide variety of specific intracellular proteins are cleaved in different cellular compartments, and it is thought that their breakdown ultimately leads to Summary the characteristic morphological changes of apoptosis (Nicholson and Thornberry, 1997). The activation of cas- We have identified a Drosophila homolog of Apaf-1 pases appears to be tightly controlled by both positive and ced-4, termed hac-1. Like mammalian APAF-1, HAC-1 can activate caspases in a dATP-dependent and negative regulators. On the one hand, members of manner in vitro. During embryonic development, hac-1 the IAP (inhibitor of apoptosis protein) family can inhibit is prominently expressed in regions where cells un- caspases and apoptosis in a variety of insect and verte- dergo natural death. Significantly, hac-1 transcription brate systems (Uren et al., 1998; Deveraux and Reed, is also rapidly induced upon ionizing irradiation, similar 1999). On the other hand, caspase activation is stimu- to the proapoptotic gene reaper. -
Manner Via Caspase-8 in an RIP3
Cutting Edge: FAS (CD95) Mediates Noncanonical IL-1 β and IL-18 Maturation via Caspase-8 in an RIP3-Independent Manner This information is current as of October 2, 2021. Lukas Bossaller, Ping-I Chiang, Christian Schmidt-Lauber, Sandhya Ganesan, William J. Kaiser, Vijay A. K. Rathinam, Edward S. Mocarski, Deepa Subramanian, Douglas R. Green, Neal Silverman, Katherine A. Fitzgerald, Ann Marshak-Rothstein and Eicke Latz Downloaded from J Immunol 2012; 189:5508-5512; Prepublished online 9 November 2012; doi: 10.4049/jimmunol.1202121 http://www.jimmunol.org/content/189/12/5508 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2012/11/12/jimmunol.120212 Material 1.DC1 References This article cites 30 articles, 9 of which you can access for free at: http://www.jimmunol.org/content/189/12/5508.full#ref-list-1 by guest on October 2, 2021 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. -
The Role of Cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies
Hindawi Publishing Corporation International Journal of Cell Biology Volume 2010, Article ID 215158, 21 pages doi:10.1155/2010/215158 Review Article TheRoleofCyclooxygenase-2inCellProliferationandCell Death in Human Malignancies Cyril Sobolewski,1 Claudia Cerella,1 Mario Dicato,1 Lina Ghibelli,2 and Marc Diederich1 1 LaboratoiredeBiologieMol´eculaire et Cellulaire du Cancer, Hopitalˆ Kirchberg, 9 rue Edward Steichen, 2540 Luxembourg, Luxembourg 2 Dipartimento di Biologia, Universita` di Roma di Roma Tor Vergata, Via Ricerca Scientifica snc, 00133 Rome, Italy Correspondence should be addressed to Marc Diederich, [email protected] Received 16 July 2009; Accepted 18 December 2009 Academic Editor: Simone Fulda Copyright © 2010 Cyril Sobolewski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. It is well admitted that the link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways, which act during the different steps of tumorigenesis. The cyclooxygenases (COXs) are a family of enzymes, which catalyze the rate-limiting step of prostaglandin biosynthesis. This family contains three members: ubiquitously expressed COX- 1, which is involved in homeostasis; the inducible COX-2 isoform, which is upregulated during both inflammation and cancer; and COX-3, expressed in brain and spinal cord, whose functions remain to be elucidated. COX-2 was described to modulate cell proliferation and apoptosis mainly in solid tumors, that is, colorectal, breast, and prostate cancers, and, more recently, in hematological malignancies. These findings prompt us to analyze here the effects of a combination of COX-2 inhibitors together with different clinically used therapeutic strategies in order to further improve the efficiency of future anticancer treatments. -
HDAC Inhibition Activates the Apoptosome Via Apaf1 Upregulation
Buurman et al. Eur J Med Res (2016) 21:26 DOI 10.1186/s40001-016-0217-x European Journal of Medical Research RESEARCH Open Access HDAC inhibition activates the apoptosome via Apaf1 upregulation in hepatocellular carcinoma Reena Buurman, Maria Sandbothe, Brigitte Schlegelberger and Britta Skawran* Abstract Background: Histone deacetylation, a common hallmark in malignant tumors, strongly alters the transcription of genes involved in the control of proliferation, cell survival, differentiation and genetic stability. We have previously shown that HDAC1, HDAC2, and HDAC3 (HDAC1–3) genes encoding histone deacetylases 1–3 are upregulated in primary human hepatocellular carcinoma (HCC). The aim of this study was to characterize the functional effects of HDAC1–3 downregulation and to identify functionally important target genes of histone deacetylation in HCC. Methods: Therefore, HCC cell lines were treated with the histone deacetylase inhibitor (HDACi) trichostatin A and by siRNA-knockdown of HDAC1–3. Differentially expressed mRNAs were identified after siRNA-knockdown of HDAC1–3 using mRNA expression profiling. Findings were validated after siRNA-mediated silencing of HDAC1–3 using qRTPCR and Western blotting assays. Results: mRNA profiling identified apoptotic protease-activating factor 1 (Apaf1) to be significantly upregulated after HDAC inhibition (HLE siRNA#1/siRNA#2 p < 0.05, HLF siRNA#1/siRNA#2 p < 0.05). As a component of the apoptosome, a caspase-activating complex, Apaf1 plays a central role in the mitochondrial caspase activation pathway of apopto- sis. Using annexin V, a significant increase in apoptosis could also be shown in HLE (siRNA #1 p 0.0034) and HLF after siRNA against HDAC1–3 (Fig. -
Biochemical Society Focused Meetings Proteases A
ORE Open Research Exeter TITLE Proteases and caspase-like activity in the yeast Saccharomyces cerevisiae. AUTHORS Wilkinson, D; Ramsdale, M JOURNAL Biochemical Society Transactions DEPOSITED IN ORE 18 November 2013 This version available at http://hdl.handle.net/10871/13957 COPYRIGHT AND REUSE Open Research Exeter makes this work available in accordance with publisher policies. A NOTE ON VERSIONS The version presented here may differ from the published version. If citing, you are advised to consult the published version for pagination, volume/issue and date of publication Biochemical Society Transactions (2011) XX, (XX-XX) (Printed in Great Britain) Biochemical Society Focused Meetings Proteases and caspase-like activity in the yeast Saccharomyces cerevisiae Derek Wilkinson and Mark Ramsdale1 Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, EX4 4QD Key words: Programmed cell death, apoptosis, necrosis, proteases, caspases, Saccharomyces cerevisiae. Abbreviations used: PCD, programmed cell death; ROS, reactive oxygen species; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ER, endoplasmic reticulum; MS, mass spectrometry. 1email [email protected] Abstract A variety of proteases have been implicated in yeast PCD including the metacaspase, Mca1 and the separase Esp1, the HtrA-like serine protease Nma111, the cathepsin-like serine carboxypeptideases and a range of vacuolar proteases. Proteasomal activity is also shown to have an important role in determining cell fate, with both pro- and anti-apoptotic roles. Caspase-3, -6- and -8 like activities are detected upon stimulation of yeast PCD, but not all of this activity is associated with Mca1, implicating other proteases with caspase-like activity in the yeast cell death response. -
XIAP's Profile in Human Cancer
biomolecules Review XIAP’s Profile in Human Cancer Huailu Tu and Max Costa * Department of Environmental Medicine, Grossman School of Medicine, New York University, New York, NY 10010, USA; [email protected] * Correspondence: [email protected] Received: 16 September 2020; Accepted: 25 October 2020; Published: 29 October 2020 Abstract: XIAP, the X-linked inhibitor of apoptosis protein, regulates cell death signaling pathways through binding and inhibiting caspases. Mounting experimental research associated with XIAP has shown it to be a master regulator of cell death not only in apoptosis, but also in autophagy and necroptosis. As a vital decider on cell survival, XIAP is involved in the regulation of cancer initiation, promotion and progression. XIAP up-regulation occurs in many human diseases, resulting in a series of undesired effects such as raising the cellular tolerance to genetic lesions, inflammation and cytotoxicity. Hence, anti-tumor drugs targeting XIAP have become an important focus for cancer therapy research. RNA–XIAP interaction is a focus, which has enriched the general profile of XIAP regulation in human cancer. In this review, the basic functions of XIAP, its regulatory role in cancer, anti-XIAP drugs and recent findings about RNA–XIAP interactions are discussed. Keywords: XIAP; apoptosis; cancer; therapeutics; non-coding RNA 1. Introduction X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3), baculoviral IAP repeat-containing protein 4 (BIRC4), and human IAPs like protein (hILP), belongs to IAP family which was discovered in insect baculovirus [1]. Eight different IAPs have been isolated from human tissues: NAIP (BIRC1), BIRC2 (cIAP1), BIRC3 (cIAP2), XIAP (BIRC4), BIRC5 (survivin), BIRC6 (apollon), BIRC7 (livin) and BIRC8 [2]. -
Viewing BCL2 and Cell Death Control from an Evolutionary Perspective
Cell Death and Differentiation (2018) 25, 13–20 & 2018 ADMC Associazione Differenziamento e Morte Cellulare All rights reserved 1350-9047/18 www.nature.com/cdd Review Viewing BCL2 and cell death control from an evolutionary perspective Andreas Strasser*,1,2 and David L Vaux*,1,2 The last 30 years of studying BCL2 have brought cell death research into the molecular era, and revealed its relevance to human pathophysiology. Most, if not all metazoans use an evolutionarily conserved process for cellular self destruction that is controlled and implemented by proteins related to BCL2. We propose the anti-apoptotic BCL2-like and pro-apoptotic BH3-only members of the family arose through duplication and modification of genes for the pro-apoptotic multi-BH domain family members, such as BAX and BAK1. In that way, a cell suicide process that initially evolved as a mechanism for defense against intracellular parasites was then also used in multicellular organisms for morphogenesis and to maintain the correct number of cells in adults by balancing cell production by mitosis. Cell Death and Differentiation (2018) 25, 13–20; doi:10.1038/cdd.2017.145; published online 3 November 2017 How are the initiators of apoptosis, the BH3-only proteins, regulated? How should BH3 mimetic drugs be combined with other cancer therapies? Will MCL1 inhibitors have a useful therapeutic index? All living things are made of cells, and each of them carries the genetic material needed for their reproduction. Generation after generation, the genomes of our ancestors were refined through natural selection to allow all of them, without exception, to survive long enough to reproduce. -
Serine Proteases with Altered Sensitivity to Activity-Modulating
(19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants. -
The Role of Caspase-2 in Regulating Cell Fate
cells Review The Role of Caspase-2 in Regulating Cell Fate Vasanthy Vigneswara and Zubair Ahmed * Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; [email protected] * Correspondence: [email protected] Received: 15 April 2020; Accepted: 12 May 2020; Published: 19 May 2020 Abstract: Caspase-2 is the most evolutionarily conserved member of the mammalian caspase family and has been implicated in both apoptotic and non-apoptotic signaling pathways, including tumor suppression, cell cycle regulation, and DNA repair. A myriad of signaling molecules is associated with the tight regulation of caspase-2 to mediate multiple cellular processes far beyond apoptotic cell death. This review provides a comprehensive overview of the literature pertaining to possible sophisticated molecular mechanisms underlying the multifaceted process of caspase-2 activation and to highlight its interplay between factors that promote or suppress apoptosis in a complicated regulatory network that determines the fate of a cell from its birth and throughout its life. Keywords: caspase-2; procaspase; apoptosis; splice variants; activation; intrinsic; extrinsic; neurons 1. Introduction Apoptosis, or programmed cell death (PCD), plays a pivotal role during embryonic development through to adulthood in multi-cellular organisms to eliminate excessive and potentially compromised cells under physiological conditions to maintain cellular homeostasis [1]. However, dysregulation of the apoptotic signaling pathway is implicated in a variety of pathological conditions. For example, excessive apoptosis can lead to neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, whilst insufficient apoptosis results in cancer and autoimmune disorders [2,3]. Apoptosis is mediated by two well-known classical signaling pathways, namely the extrinsic or death receptor-dependent pathway and the intrinsic or mitochondria-dependent pathway. -
Caspase-1 Antibody A
Revision 1 C 0 2 - t Caspase-1 Antibody a e r o t S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 5 2 Web: [email protected] 2 www.cellsignal.com 2 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source: UniProt ID: Entrez-Gene Id: WB H Endogenous 20 p20. 30 to 45 Rabbit P29466 834 beta, delta, gamma. 50 alpha. Product Usage Information 3. Miura, M. et al. (1993) Cell 75, 653-60. 4. Kuida, K. et al. (1995) Science 267, 2000-3. Application Dilution 5. Li, P. et al. (1995) Cell 80, 401-11. 6. Feng, Q. et al. (2004) Genomics 84, 587-91. Western Blotting 1:1000 7. Martinon, F. et al. (2002) Mol Cell 10, 417-26. Storage Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody. Specificity / Sensitivity Caspase-1 Antibody detects endogenous levels of pro-caspase-1 and the caspase-1 p20 subunit. The antibody is expected to detect alpha, beta, gamma and delta isoforms. Species Reactivity: Human Source / Purification Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues within the p20 subunit of human caspase-1. Antibodies are purified by protein A and peptide affinity chromatography. Background Caspase-1, or interleukin-1ß converting enzyme (ICE/ICEα), is a class I cysteine protease, which also includes caspases -4, -5, -11, and -12. -
Supplementary Material DNA Methylation in Inflammatory Pathways Modifies the Association Between BMI and Adult-Onset Non- Atopic
Supplementary Material DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non- Atopic Asthma Ayoung Jeong 1,2, Medea Imboden 1,2, Akram Ghantous 3, Alexei Novoloaca 3, Anne-Elie Carsin 4,5,6, Manolis Kogevinas 4,5,6, Christian Schindler 1,2, Gianfranco Lovison 7, Zdenko Herceg 3, Cyrille Cuenin 3, Roel Vermeulen 8, Deborah Jarvis 9, André F. S. Amaral 9, Florian Kronenberg 10, Paolo Vineis 11,12 and Nicole Probst-Hensch 1,2,* 1 Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; [email protected] (A.J.); [email protected] (M.I.); [email protected] (C.S.) 2 Department of Public Health, University of Basel, 4001 Basel, Switzerland 3 International Agency for Research on Cancer, 69372 Lyon, France; [email protected] (A.G.); [email protected] (A.N.); [email protected] (Z.H.); [email protected] (C.C.) 4 ISGlobal, Barcelona Institute for Global Health, 08003 Barcelona, Spain; [email protected] (A.-E.C.); [email protected] (M.K.) 5 Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain 6 CIBER Epidemiología y Salud Pública (CIBERESP), 08005 Barcelona, Spain 7 Department of Economics, Business and Statistics, University of Palermo, 90128 Palermo, Italy; [email protected] 8 Environmental Epidemiology Division, Utrecht University, Institute for Risk Assessment Sciences, 3584CM Utrecht, Netherlands; [email protected] 9 Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College, SW3 6LR London, UK; [email protected] (D.J.); [email protected] (A.F.S.A.) 10 Division of Genetic Epidemiology, Medical University of Innsbruck, 6020 Innsbruck, Austria; [email protected] 11 MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, W2 1PG London, UK; [email protected] 12 Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy * Correspondence: [email protected]; Tel.: +41-61-284-8378 Int. -
Proteases to Die For
Downloaded from genesdev.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Proteases to die for Vincent Cryns1 and Junying Yuan2,3 1Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University School of Medicine, Chicago, Illinois 60611 USA; 2Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115 USA Apoptosis or programmed cell death (PCD) is a geneti- have identified two genes (ced-3 and ced-4) that are each cally regulated, cellular suicide mechanism that plays a required for the execution of cell death and one (ced-9) crucial role in development and in the defense of homeo- that inhibits cell death (Hengartner et al. 1992; Yuan and stasis. Cells respond to a variety of disparate signals by Horvitz 1992; Yuan et al. 1993). Mutational analyses of committing suicide through a series of dramatic but re- these genes in C. elegans have defined a sequential cell markably uniform events. Morphologically, cells under- death pathway. Inactivating mutations of ced-9 result in going apoptosis demonstrate nuclear/cytoplasmic con- inappropriate cell deaths, but only if both ced-3 and densation and membrane protrusions. These initial ced-4 are functional (Hengartner et al. 1992). Targeted changes are followed by fragmentation of the nuclear overexpression of either ced-4 or ced-3 induces cell contents and subsequent encapsulation of these frag- death, these cell deaths are inhibited by ced-9. In trans- ments into ‘‘apoptotic bodies’’ that are quickly and un- genic worms, maximal cell death induced by ced-4 over- obtrusively consumed by adjacent cells, thereby leaving expression requires ced-3, whereas ced-3-mediated cell little trace of the apoptotic cell’s prior existence (Kerr et death is independent of ced-4.