A system model for cell death using Fuzzy and SPICE

A family of cystein-dependent aspartate-directed proteases, called caspases, is responsible for the proteolytic cleavage of cellular proteins leading to the characteristic apoptotic features, e.g. cleavage of caspase-activated DNase resulting in inter nucleosomal DNA fragmentation. Currently, two pathways for activating caspases have been studied in detail. One starts with ligation of a death ligand to its transmembrane death receptor, followed by recruitment and activation of caspases in the death-inducing signaling complex. The second pathway involves the participation of mitochondria, which release caspase-activating proteins into the cytosol, thereby forming the apoptosome where caspases will bind and become activated. In addition, two other apoptotic pathways are emerging: endoplasmic reticulum stress-induced apoptosis and caspase-independent apoptosis. The model for cell death has been implemented using Fuzzy and CMOS logic using SPICE taking three input signals: Tumor necrosis factor-α (TNF), Epidermal growth factor (EGF) and Insulin.

[1]  Eileen D. Adamson,et al.  Epidermal growth factor receptors , 1981, Molecular and Cellular Biochemistry.

[2]  Ron Weiss,et al.  Toward in vivo Digital Circuits , 2002 .

[3]  D. Lauffenburger,et al.  A Systems Model of Signaling Identifies a Molecular Basis Set for Cytokine-Induced Apoptosis , 2005, Science.

[4]  K. Vermeulen,et al.  Apoptosis: mechanisms and relevance in cancer , 2005, Annals of Hematology.

[5]  J Downward,et al.  Interaction of Ras and Raf in intact mammalian cells upon extracellular stimulation. , 1994, The Journal of biological chemistry.

[6]  Abbreviations , 1971 .

[7]  T. Libermann,et al.  Expression of epidermal growth factor receptors in human brain tumors. , 1984, Cancer research.

[8]  W. Jarvis,et al.  Caspase-9 regulation: An update , 2004, Apoptosis.

[9]  M. White,et al.  The insulin signalling system and the IRS proteins , 1997, Diabetologia.

[10]  Olivier Hermine,et al.  Vital functions for lethal caspases , 2005, Oncogene.

[11]  Dario R. Alessi,et al.  The insulin signalling pathway , 2002, Current Biology.

[12]  N. K. Sah,et al.  Mitochondria can power cells to life and death , 2000 .

[13]  F. Cecconi,et al.  Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax/Bak‐mediated permeabilization , 2003, The EMBO journal.

[14]  T. Fan,et al.  Apoptosis-inducing factor and apoptosis. , 2003, Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica.

[15]  T. Fan,et al.  Caspase family proteases and apoptosis. , 2005, Acta biochimica et biophysica Sinica.

[16]  Jongkyeong Chung,et al.  Akt: versatile mediator of cell survival and beyond. , 2002, Journal of biochemistry and molecular biology.

[17]  N. Normanno,et al.  Epidermal growth factor receptor (EGFR) signaling in cancer. , 2006, Gene.

[18]  M. Hung,et al.  EGFR signaling pathway in breast cancers: from traditional signal transduction to direct nuclear translocalization , 2006, Breast Cancer Research and Treatment.

[19]  J. Lotem,et al.  Cytokines as suppressors of apoptosis , 1999, Apoptosis.

[20]  D. Lauffenburger,et al.  A Compendium of Signals and Responses Triggered by Prodeath and Prosurvival Cytokines*S , 2005, Molecular & Cellular Proteomics.

[21]  Weixin Zhou,et al.  STAT3 in EGF Receptor-Mediated Fibroblast and Human Prostate Cancer Cell Migration, Invasion and Apoptosis. , 2006 .