{"database":"Cell Collective","file_versions":[],"scores":{"citationCount":16877,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"omics_type":["Models"],"submitter":["Tomas Helikar"],"version_name":[""],"full_dataset_link":["https://cellcollective.org/#2135/yeast-apoptosis"],"model_score":["47.961000000000006"],"default_version":["1"],"ModelFormat":["SBML"],"submitter_affiliation":[""],"submitter_email":[""],"version_id":["1"],"repository":["Cell Collective"],"version_url":["https://cellcollective.org/#2135:1/yeast-apoptosis"],"version_description":[""],"pubmed_abstract":["Programmed cell death (PCD) is an essential cellular mechanism that is evolutionary conserved, mediated through various pathways and acts by integrating different stimuli. Many diseases such as neurodegenerative diseases and cancers are found to be caused by, or associated with, regulations in the cell death pathways. Yeast Saccharomyces cerevisiae, is a unicellular eukaryotic organism that shares with human cells components and pathways of the PCD and is therefore used as a model organism. Boolean modeling is becoming promising approach to capture qualitative behavior and describe essential properties of such complex networks. Here we present large literature-based and to our knowledge first Boolean model that combines pathways leading to apoptosis (a type of PCD) in yeast. Analysis of the yeast model confirmed experimental findings of anti-apoptotic role of Bir1p and pro-apoptotic role of Stm1p and revealed activation of the stress protein kinase Hog proposing the maximal level of activation upon heat stress. In addition we extended the yeast model and created an in silico humanized yeast in which human pro- and anti-apoptotic regulators Bcl-2 family and Valosin-contain protein (VCP) are included in the model. We showed that accumulation of Bax in silico humanized yeast shows apoptotic markers and that VCP is essential target of Akt Signaling. The presented Boolean model provides comprehensive description of yeast apoptosis network behavior. Extended model of humanized yeast gives new insights of how complex human disease like neurodegeneration can initially be tested."],"pubmed_title":["Boolean model of yeast apoptosis as a tool to study yeast and human apoptotic regulations."],"pubmed_authors":["Kazemzadeh Laleh L, Cvijovic Marija M, Petranovic Dina D"],"description_synonyms":["Drob-1/Debcl/dBORG-1, Carnitine uptake deficiency, Kinship, Neurologic Diseases, A4, sci, CG17228, Drob-1/Debcl/dBorg-1/dBok, AKT signalling cascade, 1135/09, ter, Hog, 1135/07, borg1/debcl, Dextrocardia-bronchiectasis-sinusitis syndrome, Neurologic Disorders, Drob-1/Debcl/dBorg-1/DBok, Programmed, Hot, debok, AA959943, symptoms, 0451/09, HOW, How, RCD, Life Cycle, myd, DmTER94, CILD1, hog, gamma sarcoglycan, 0244/09, CILD2, CILD3, Degenerative Condition, TERA, Kinship Network, I, 15S Mg(2+)-ATPase p97 subunit, dvcp, DROPROSA, stru, Saccharomyes cerevisiae, Mbp-1, AKT signaling cascade, l(3)S053606, Primary systemic carnitine deficiency, p97/VCP, Saccharomyces uvarum var. melibiosus, PKB signaling cascade, 671/2, PKB signalling cascade, Intrinsic Pathway Apoptosis, Degenerative Neurologic Disease, Role Concepts, ter94, dVCP, Homo sapiens disease, Mycoderma cerevisiae, protein kinase B signal transduction, NKX3.1, Acta-2, screening, dBORG-1/DROB-1/DEBCL/dBOK, BG1, Dimerization cofactor of HNF1, Heat Shock Protein, Actsk-1, CG2331, Acceptance Processes, CSBP, Baker's Yeasts, dmTERA, signaling (initiator) caspase activity, Role Concept, Tera, induction of apoptosis, Saccharomyces diastaticus, Siewert syndrome, mKIAA0609, 1316/02, PCD, Pcd, Role, BcDNA:HL08040, sarcoglycan, xBax, Caspase-Dependent, activation, Bcl-2, fg, Debcl/dBorg-1/dBok/Drob-1, whole organism, Degenerative Diseases, bronchiectasis, 1167/13, HEL-220, expanded, signs, Ciliary Motility, Neurologic Disease, Neurodegenerative disease, human, experimental procedures, Intrinsic Pathway Apoptoses, Saccharomyces cerevisiae (Desm.) Meyen ex E.C. 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signaling, findings, NKX3A, Family Research, 35 kDa dystrophin-associated glycoprotein, body, Proteins, disorders, whole body, Phenylalanine hydroxylase-stimulating protein, Primary, qkr, l(3)S090417, Cell, Saccaromyces cerevisiae, SGCG, BOK, Bok, Concept, Family Members, Sccharomyces cerevisiae, l(3)rL433, l(3)rI160, Temperatures, native protein, 0441/16, KH93F, chemical analysis, Pcbd, condition, Death, BcDNA.GM02885, protein kinase B signaling cascade, ATCMPG1, MET, ATCMPG2, Saccharomyces oviformis, Nkx-3.1, apoptosis, DMDA1, Ciliary Dyskinesias, 3110001E05, Neurologic Degenerative Conditions, CDC48, CSPB1, BcDNA:LP07248, Classic Apoptoses, l(3)rK204, Gene Proteins, D830018M01Rik, CRK1, Families, apoptotic program, Stress, commitment to apoptosis, Central Nervous System, D630044D05Rik, Baker's Yeast, Relatives, Carnitine transporter defect, l(3)rK137, Networks, MGC130048, KTGNR, Ciliary Dyskinesia, determination, caspase-independent cell death, DmelCG32595, Mbp1, CUD, Ter94, 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anon-EST:Liang-2.39, dbok, TER ATPase, Classical, Apoptoses, HEL-S-70, other disease, human being, SGCG_HUMAN, Family Member, chronic sinusitis and dextrocardia syndrome, experimental, P62, Kartagener type, caspase-dependent programmed cell death, dbok/debcl, Brewer's, Caspase Dependent Apoptosis, baker's yeast, Gene, Network, PKB signaling, CG1963, cerebral degeneration disease, TYPE, froggy, Gyltl1a, l(3)10419, DAGA4, 7.12, dmTAF8, p38Hog, Homo sapiens, debcl/Borg1, Pterin carbinolamine dehydratase, 35DAG, HL-VIII, anon-WO0140519.15, non-apoptotic programmed cell death, F15E12.6, Type I, VCP ATPase, SCG3, VCP, Vcp, PROS, Nervous System, methods, 0585/13, Heat Shock Proteins, l(3)s2612, Research, experimental section, CG7128, LARGE, apoptosis activator activity, Stress Protein, Neurodegenerative Disorders, Dyskinesia, non-neoplastic, BPFD#36, prod, Candida robusta, dTERA, Disorder, great, AW986256, DmelCG10293, disorder, 1883, dborg1, xbcl2, Kinship Networks, Behaviors, TAF, 0563/18, Family, TCF1, cdc48, protein kinase B signalling cascade, Immotile Cilia Syndromes, Saccharomyces cerevisiae 'var. diastaticus', protein complex, clone 2.39, p97, medical condition, IBMPFD1, LGMD2C, l(3)rJ806, Pros, Degenerative Neurologic Disorder, Debcl/dBorg-1/dRob-1, DmelCG1963, HL1, Programmed Cell Death, Protein, TFIID, DIC1, pTER94, Heat-Shock Protein, who, apoptosis signaling, Degenerative Conditions, Acceptance, Temperature, Mxi2, DEBCL, Sapk2A, Who/How, C430015F12Rik, l(2)46Ch, Protein Gene Products, Deficiency of plasma-membrane carnitine transporter, Primary Ciliary, DmelCG7128, Debcl, l(2)46CFs, Modern Man, SCARMD2, qkr[93F], Neurodegenerative Disease, assay, TAF8, Bax, l(2)46CFf, Baker Yeast"],"pubmed_title_synonyms":["human being, Caspase-Dependent Apoptosis, Modern, caspase-dependent programmed cell death, baker's yeast, Caspase Dependent Apoptosis, type I programmed cell death, Saccharomyces italicus, Saccaromyces cerevisiae, activation of apoptosis, Human, Sccharomyces cerevisiae, signaling (initiator) caspase activity, induction of apoptosis, Extrinsic Pathway Apoptoses, Homo sapiens, Intrinsic Pathway, Programmed Cell Death, Extrinsic Pathway Apoptosis, yeast, Type I, Caspase-Dependent, human., Man, lager beer yeast, Saccharomyces oviformis, apoptosis signaling, study, Yeast, Man (Taxonomy), apoptosis, Saccharomyes cerevisiae, Saccharomyces uvarum var. melibiosus, apoptosis activator activity, Classic Apoptoses, Intrinsic Pathway Apoptoses, Intrinsic Pathway Apoptosis, Candida robusta, induction of apoptosis by p53, Saccharomyces capensis, Classic, Classic Apoptosis, apoptotic program, Modern Man, Classical Apoptosis, Extrinsic Pathway, commitment to apoptosis, brewer's yeast, Classical, Apoptoses, Apoptosis"],"name_synonyms":["Saccharomyces oviformis, apoptosis signaling, Yeast, Caspase-Dependent Apoptosis, apoptosis, caspase-dependent programmed cell death, Saccharomyes cerevisiae, baker's yeast, Caspase Dependent Apoptosis, Saccharomyces uvarum var. melibiosus, type I programmed cell death, apoptosis activator activity, Saccharomyces italicus, Saccaromyces cerevisiae, activation of apoptosis, Classic Apoptoses, Intrinsic Pathway Apoptoses, commitment to apoptosis., Sccharomyces cerevisiae, Intrinsic Pathway Apoptosis, Candida robusta, signaling (initiator) caspase activity, induction of apoptosis, induction of apoptosis by p53, Extrinsic Pathway Apoptoses, Saccharomyces capensis, Intrinsic Pathway, Classic, Classic Apoptosis, apoptotic program, Programmed Cell Death, Extrinsic Pathway Apoptosis, yeast, Classical Apoptosis, Extrinsic Pathway, brewer's yeast, Type I, Caspase-Dependent, Classical, Apoptoses, lager beer yeast, Apoptosis"],"pubmed_abstract_synonyms":["Drob-1/Debcl/dBORG-1, Carnitine uptake deficiency, Kinship, Neurologic Diseases, A4, sci, Tumor, CG17228, Drob-1/Debcl/dBorg-1/dBok, AKT signalling cascade, 1135/09, ter, Hog, 1135/07, borg1/debcl, Dextrocardia-bronchiectasis-sinusitis syndrome, Neurologic Disorders, Drob-1/Debcl/dBorg-1/DBok, Programmed, debok, AA959943, symptoms, 0451/09, HOW, How, RCD, Life Cycle, Kinase, myd, DmTER94, CILD1, hog, gamma sarcoglycan, 0244/09, CILD2, CILD3, Degenerative Condition, TERA, Kinship Network, I, 15S Mg(2+)-ATPase p97 subunit, dvcp, DROPROSA, stru, Saccharomyes cerevisiae, Mbp-1, AKT signaling cascade, l(3)S053606, Primary systemic carnitine deficiency, p97/VCP, Saccharomyces uvarum var. melibiosus, PKB signaling cascade, 671/2, PKB signalling cascade, Intrinsic Pathway Apoptosis, Degenerative Neurologic Disease, Role Concepts, ter94, dVCP, Homo sapiens disease, Mycoderma cerevisiae, protein kinase B signal transduction, NKX3.1, Tumors, Acta-2, screening, dBORG-1/DROB-1/DEBCL/dBOK, BG1, Dimerization cofactor of HNF1, Actsk-1, CG2331, Acceptance Processes, CSBP, Baker's Yeasts, dmTERA, Benign, signaling (initiator) caspase activity, Role Concept, Tera, induction of apoptosis, Saccharomyces diastaticus, Siewert syndrome, mKIAA0609, 1316/02, PCD, Pcd, Role, BcDNA:HL08040, sarcoglycan, xBax, Caspase-Dependent, activation, Bcl-2, fg, Debcl/dBorg-1/dBok/Drob-1, whole organism, Degenerative Diseases, bronchiectasis, 1167/13, HEL-220, expanded, signs, Ciliary Motility, Benign Neoplasms, Neurologic Disease, Neurodegenerative disease, human, Malignant Neoplasms, Intrinsic Pathway Apoptoses, Saccharomyces cerevisiae (Desm.) Meyen ex E.C. 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0671/02, l(3)j12C8, Neurologic Disorder, AKT signaling, findings, NKX3A, Malignant Neoplasm, Family Research, 35 kDa dystrophin-associated glycoprotein, body, Proteins, disorders, whole body, Phenylalanine hydroxylase-stimulating protein, Primary, qkr, l(3)S090417, Cell, Saccaromyces cerevisiae, SGCG, BOK, Bok, Concept, Family Members, Sccharomyces cerevisiae, l(3)rL433, SRK2D, l(3)rI160, native protein, 0441/16, KH93F, chemical analysis, Pcbd, Neoplasm, condition, Death, BcDNA.GM02885, protein kinase B signaling cascade, ATCMPG1, MET, ATCMPG2, Saccharomyces oviformis, Nkx-3.1, apoptosis, DMDA1, Ciliary Dyskinesias, 3110001E05, Neurologic Degenerative Conditions, CDC48, Cancers, CSPB1, BcDNA:LP07248, Classic Apoptoses, l(3)rK204, Gene Proteins, D830018M01Rik, CRK1, Families, apoptotic program, commitment to apoptosis, Central Nervous System, D630044D05Rik, Baker's Yeast, PROTEIN KINASE, Relatives, Neoplasia, Carnitine transporter defect, l(3)rK137, Networks, MGC130048, KTGNR, Ciliary Dyskinesia, determination, caspase-independent cell death, DmelCG32595, Mbp1, CUD, Ter94, Neurologic Degenerative Condition, protein, PPP1R50, type I programmed cell death, ALS14, bax-A, Neurodegenerative Diseases, DmelCG2331, Extrinsic Pathway Apoptoses, diseases, Primary ciliary dyskinesia and situs inversus, Roles, DNAHC5, Concepts, diseases and disorders, protein aggregate, animal, RK, l(3)j5D5, 4.2.1.96, Family Life Cycle, bagpipe, Nervous System Degenerative Diseases, 24B, human disease, Man (Taxonomy), Primary Ciliary Dyskinesia, MUB3_18, Baker, MUB3.18, l(3)j6E2, dBrog-1, Neurodegenerative Disorder, CG10293, nonapoptotic programmed cell death, Acts, CG33134, debc1, C19orf51, IBMPFD, l(3)j5B5, 0320/10, DMPROSPER, DCoH, l(2)03775, xlbax, Saccharomyces capensis, 22.26, Classic, Classical Apoptosis, Neurologic Degenerative Disease, Baker's, gamma-sarcoglycan, Malignancies, necrosis, Dextrocardia bronchiectasis and sinusitis, brewer's yeast, Family Life Cycles, ICS, single-organism behavior, AKT signal transduction, 0904/17, DCOH, Caspase-Dependent Apoptosis, Process, l(3)rO534, gyltl1b-b, PRO, Pro, Modern, SG-gamma, PF22, Ciliary, Primary ciliary dyskinesia, dBok, dBOK, Dcoh, CYS, Literatures, 3.6.4.6, bcl-2, organism, Acceptance Process, PROS-1, PROS-2, dBorg01, Immotile cilia syndrome, Intrinsic Pathway, SZ1, MDDGA6, pro, Extrinsic Pathway Apoptosis, DmelCG33134, Diseases, protein kinase B signaling, Progressive neurodegenerative disorder, BcDNA:GM02885, KIAA0609, Filiation, and GLY protein 2, Valosin-containing protein, Yeast, Epistemology, and GLY protein 1, DBok, Immotile Cilia Syndrome, gyltl1b, Voila, 0664/07, mdc1d, p38alpha, Prkm15, p38, Cell Death, Dimerization cofactor of hepatocyte nuclear factor 1-alpha, anon-WO2004063362.65, gamma (35kDa dystrophin-associated glycoprotein), Dbok, TAF[[II]], Prkm14, anon-WO2004063362.67, CG12397, ciliary dyskinesia primary, Life Cycles, disease, SNF1-RELATED PROTEIN KINASE 2-2, DMDA, Drob-1, induction of apoptosis by p53, VCP/p97, enlarged, Debcl/Drob-1/dBorg-1/dBok, Degenerative, caspase-independent apoptosis, anon-EST:Liang-2.39, dbok, TER ATPase, Classical, Protein Kinase, Apoptoses, HEL-S-70, other disease, human being, SGCG_HUMAN, Family Member, chronic sinusitis and dextrocardia syndrome, P62, Kartagener type, caspase-dependent programmed cell death, Benign Neoplasm, dbok/debcl, Brewer's, Caspase Dependent Apoptosis, baker's yeast, Gene, Network, PKB signaling, Malignant, CG1963, cerebral degeneration disease, TYPE, froggy, Gyltl1a, l(3)10419, DAGA4, 7.12, dmTAF8, p38Hog, Homo sapiens, debcl/Borg1, Pterin carbinolamine dehydratase, 35DAG, HL-VIII, anon-WO0140519.15, non-apoptotic programmed cell death, F15E12.6, Type I, VCP ATPase, SCG3, VCP, Vcp, PROS, Nervous System, 0585/13, l(3)s2612, Malignancy, Research, CG7128, LARGE, apoptosis activator activity, Neurodegenerative Disorders, ATP-protein phosphotransferase, Dyskinesia, non-neoplastic, BPFD#36, prod, SNRK2-2, Candida robusta, dTERA, Disorder, great, AW986256, DmelCG10293, disorder, 1883, dborg1, xbcl2, Kinship Networks, Behaviors, TAF, 0563/18, Family, TCF1, cdc48, protein kinase B signalling cascade, Immotile Cilia Syndromes, Saccharomyces cerevisiae 'var. diastaticus', protein complex, clone 2.39, p97, medical condition, IBMPFD1, LGMD2C, l(3)rJ806, Pros, Degenerative Neurologic Disorder, Debcl/dBorg-1/dRob-1, DmelCG1963, HL1, Programmed Cell Death, Protein, TFIID, DIC1, pTER94, who, apoptosis signaling, Degenerative Conditions, Acceptance, SPK-2-2, Kinases, Mxi2, DEBCL, Sapk2A, Who/How, C430015F12Rik, l(2)46Ch, Protein Gene Products, Deficiency of plasma-membrane carnitine transporter, Primary Ciliary, DmelCG7128, Debcl, l(2)46CFs, Modern Man, SCARMD2, qkr[93F], Neurodegenerative Disease, assay, TAF8, Bax, l(2)46CFf, Baker Yeast"],"citation_count":["16877"],"additional_accession":[]},"is_claimable":false,"name":"Yeast Apoptosis","description":"Programmed cell death (PCD) is an essential cellular mechanism that is evolutionary conserved, mediated through various pathways and acts by integrating different stimuli. Many diseases such as neurodegenerative diseases and cancers are found to be caused by, or associated with, regulations in the cell death pathways. Yeast Saccharomyces cerevisiae, is a unicellular eukaryotic organism that shares with human cells components and pathways of the PCD and is therefore used as a model organism. Boolean modeling is becoming promising approach to capture qualitative behavior and describe essential properties of such complex networks. Here we present large literature-based and to our knowledge first Boolean model that combines pathways leading to apoptosis (a type of PCD) in yeast. Analysis of the yeast model confirmed experimental findings of anti-apoptotic role of Bir1p and pro-apoptotic role of Stm1p and revealed activation of the stress protein kinase Hog proposing the maximal level of activation upon heat stress. In addition we extended the yeast model and created an in silico humanized yeast in which human pro- and anti-apoptotic regulators Bcl-2 family and Valosin-contain protein (VCP) are included in the model. We showed that accumulation of Bax in silico humanized yeast shows apoptotic markers and that VCP is essential target of Akt Signaling. The presented Boolean model provides comprehensive description of yeast apoptosis network behavior. Extended model of humanized yeast gives new insights of how complex human disease like neurodegeneration can initially be tested.","dates":{"created":"2013-06-04","publication":"","submission":"2018-04-18","last_modified":"2018-04-18"},"accession":"2135","cross_references":{"pubmed":["23233838"]}}