BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=Diedrichs2018.cpshttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703.scihttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000703?filename=BIOMD0000000703.xppprimaryOK200Danilo R. DiedrichsManually curatedL2V4https://www.ebi.ac.uk/biomodels/BIOMD000000070329668363falseBioModelsSBMLModelsDiedrichs2018 A data entrained computational model for testing the regulatory logic of the vertebrate unfolded protein response2018MODEL1803300000Diedrichs DR, Gomez JA, Huang CS, Rutkowski DT, Curtu ODiedrichs DR29668363,
The vertebrate unfolded protein response (UPR) is characterized by multiple interacting nodes among its three pathways, yet the logic underlying this regulatory complexity is unclear. To begin to address this issue, we created a computational model of the vertebrate UPR that was entrained upon and then validated against experimental data. As part of this validation, the model successfully predicted the phenotypes of cells with lesions in UPR signaling, including a surprising and previously unreported differential role for the eIF2α phosphatase GADD34 in exacerbating severe stress but ameliorating mild stress. We then used the model to test the functional importance of a feedforward circuit within the PERK/CHOP axis and of cross-regulatory control of BiP and CHOP expression. We found that the wiring structure of the UPR appears to balance the ability of the response to remain sensitive to endoplasmic reticulum stress and to be deactivated rapidly by improved protein-folding conditions. This model should serve as a valuable resource for further exploring the regulatory logic of the UPR.. 12, 29.
Department of Mathematics, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242.danilo.diedrichs@wheaton.eduWheaton CollegeBIOMD0000000703The vertebrate unfolded protein response (UPR) is characterized by multiple interacting nodes among its three pathways, yet the logic underlying this regulatory complexity is unclear. To begin to address this issue, we created a computational model of the vertebrate UPR that was entrained upon and then validated against experimental data. As part of this validation, the model successfully predicted the phenotypes of cells with lesions in UPR signaling, including a surprising and previously unreported differential role for the eIF2α phosphatase GADD34 in exacerbating severe stress but ameliorating mild stress. We then used the model to test the functional importance of a feedforward circuit within the PERK/CHOP axis and of cross-regulatory control of BiP and CHOP expression. We found that the wiring structure of the UPR appears to balance the ability of the response to remain sensitive to endoplasmic reticulum stress and to be deactivated rapidly by improved protein-folding conditions. This model should serve as a valuable resource for further exploring the regulatory logic of the UPR.A data-entrained computational model for testing the regulatory logic of the vertebrate unfolded protein response.Diedrichs Danilo R DR, Gomez Javier A JA, Huang Chun-Sing CS, Rutkowski D Thomas DT, Curtu Rodica RResponse, data, Unfolded., Vertebrate, Unfolded, Unfolded Protein, Logics, Unfolded Protein Responses, Protein Response, Protein Responses, ResponsesAU019543, DmErk, IAA23, second cervical vertebra, IAA21, C|EBP-homologous protein, HEL-S-89n, IAA25, Addresses, Hsc-70-3, Hsc-3, protein, Protein Response, C|EBP-homologous protein 10, SR2-1, axis vertebra, protein polypeptide chains, Roles, Endoplasmic Reticulum Stresses, responsivity, Concepts, Heat shock 70 kDa protein 5, AUXIN RESPONSE FACTOR 7, protein aggregate, SEM, Sem, Dm-GADD34, CG1579, MAP-k, Erk/Map kinase, reference sample, hsc3, C2, DERK-A, Dsor2, proteins, E(sina)7, Xchop, sem, Rl, Gadd153, DmPEK, GADD34, allergic reaction, DERK, GDF-10, GRP78, vertebra 2, signaling process, Role Concepts, EIF2-like, CG4147, dERK, CG2087, Gadd34, Grp78, anon-WO0138581.7, Logics., phosphatase, hsc72, single organism signaling, hsc70, ERK-A, dpERK, dpErk, Mapk, Peg-3, Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78, dmHsc72, Erk1, D2Wsu17e, DmMAPK, C2 vertebra, dp-ERK, predicted, gadd153, l(1)G0466, l(1)G0102, Role Concept, l(1)G0341, ER stress, MapK, MAPK, Responses, Role, pMAPK, pMapK, Hsc3, HSC3, mapk, ARF7, DmelCG2087, l(1)G0111, Myd116, ERKa, RGD1624209, DmERKA, DmelCG4147, rl/MAPK, BcDNA:RE08694, Sez7, BiP, PERK, Endoplasmic Reticulum, l(2R)EMS45-39, DPERK, DmelCG12559, dGADD34, MSG1, l(2)41Ac, BMP-3B, WRS, axis [C II], perk, experimental procedures, DpERK, DpErk, Phenotypes, ErkA, ERKA, CT34260, dpERk, Bip, BIP, hypersensitivity reaction disease, Reticulum Stresses, C|EBP zeta, Pek, PEK, HSC70-3, pERK, biological signaling, bip, Logics, experimental, 9630030H21, GroupII, conformation, mBiP, 12559, stalk, CHOP, Hsc3p, baffled, protein-containing complex, NON-PHOTOTROPHIC HYPOCOTYL, EK2-1, Stresses, AI427929, chop, D2Wsu141e, polypeptide chain, Perk, Growth arrest and DNA-damage-inducible protein GADD153, AL022860, sensitive, DmelCG3825, Growth arrest and DNA damage-inducible protein GADD153, MJC20.12, MASSUGU 1, Steroidogenesis-activator polypeptide, Hsce70, GRP-78, sensitivity, CCAAT|enhancer-binding protein homologous protein, Hsp-c3, dhsc70, Erk, ERK, SEZ-7, indole-3-acetic acid inducible 25, reactivity, methods, Unfolded Protein, MJC20_12, experimental section, axis (CII), Unfolded, indole-3-acetic acid inducible 21, CG18732, culm, Hsc70, indole-3-acetic acid inducible 23, Growth|differentiation factor 10, erk, grp78, MIF2, HSC70, Bone-inducing protein, rll, DmERK-A, hypersensitivity reaction, relational structural quality, DDIT-3, Controlled, TIR5, T1M15.130, data, Controlling, Chop10, Reticulum Stress, Unfolded Protein Responses, axis, protein complex, CT39192, Immunoglobulin heavy chain-binding protein, CG3825, l(1)G0292, Cell, Concept, HSC-70, cervical axis, hsc70-3, native protein, natural protein, Protein, BIPOSTO, Vertebrate, T1M15_130, hypersensitivity, TRANSPORT INHIBITOR RESPONSE 5, AUXIN-RESPONSIVE TRANSCRIPTIONAL ACTIVATOR 7, hypersensitive, CG12559, Su(Raf)2B, cervical vertebra 2, dpERK1, phosphoric monoester hydrolase activity, CHOP10, EY2-2, GADD153, CHOP-10, signalling, AUXIN-REGULATED TRANSCRIPTIONAL ACTIVATOR 7, D-ERK, Endoplasmic, signalling process, dpMAPK, luminal binding protein, l(1)G0407, Stress, Response, gadd34, response, CEBPZ, Protein Responsesextent, APR, AU019543, DmErk, Public Sectors, IAA23, second cervical vertebra, Globular Protein Folding, IAA21, C|EBP-homologous protein, HEL-S-89n, IAA25, Addresses, Hsc-70-3, Hsc-3, nip, eIF-2-beta, beta-tubulin folding, EIF2G, Protein Response, DGCN2, EIF2B, C|EBP-homologous protein 10, eIF2, EIF2A, SR2-1, dmTAF[[II]]230, axis vertebra, Anniversary, Roles, responsivity, B1, l(2)SH1330, Concepts, Heat shock 70 kDa protein 5, AUXIN RESPONSE FACTOR 7, Public Enterprise, 2810026E11Rik, EIF-2A, SEM, Sem, Dm-GADD34, CG1579, MAP-k, EIF-2alpha, dGCN2, Erk/Map kinase, TFIID TAF250, reference sample, hsc3, cel, NOXA, C2, Public Domains, DERK-A, Dsor2, 35Bb, E(sina)7, Xchop, sem, Rl, Gadd153, DmPEK, Folding, GADD34, AA408636, allergic reaction, chaperonin-mediated tubulin folding, DERK, GDF-10, GRP78, vertebra 2, Dedications, signaling process, AA571381, Role Concepts, EIF2-like, EIF2, CG4147, dERK, CG2087, Gadd34, Grp78, anon-WO0138581.7, Event, phosphatase, hsc72, single organism signaling, hsc70, ERK-A, dTAF[[II]]230, dpERK, dpErk, Mapk, completeness, Peg-3, Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78, EIF2gamma, acid, dmHsc72, TAF200, Erk1, D2Wsu17e, DmMAPK, C2 vertebra, TAFII-250, dp-ERK, TAF250/230, predicted, gadd153, l(1)G0466, l(1)G0102, chaperone activity, Special Events, TAFII250, l(2)br3, l35Bb, Role Concept, l(1)G0341, Globular Protein, ER stress, co-chaperonin activity, EIF-2, MapK, Public Domain, MAPK, Responses, Role, Domains, pMAPK, pMapK, alpha-tubulin folding, Nucl, Protein Foldings, Hsc3, HSC3, mapk, ARF7, Domain, DmelCG2087, l(1)G0111, Myd116, Acid, ERKa, Special Event, RGD1624209, DmERKA, DmelCG4147, rl/MAPK, BcDNA:RE08694, Sez7, BiP, PERK, l(2R)EMS45-39, acide, DPERK, DmelCG12559, acids, dGADD34, MSG1, eIF-2, l(2)41Ac, BMP-3B, acido, WRS, axis [C II], CG17603, perk, TAF[[II]], l(2)SH2 1330, experimental procedures, DpERK, DpErk, Phenotypes, AW822225, ErkA, ERKA, CT34260, co-chaperone activity, Sector, dpERk, Globular Protein Foldings, AA986487, Bip, BIP, Taf250, SR3-5, hypersensitivity reaction disease, multichaperone pathway, 2018, C|EBP zeta, BG:DS01219.1, Pek, PEK, HSC70-3, TAF230, IGFBP3R, pERK, D0Nds28, B530004O11Rik, d230, biological signaling, Sectors, CG1609, bip, Logics, experimental, 9630030H21, GroupII, conformation, mol, mBiP, Foldings, 12559, APOER, dTAFII250, stalk, Copyrights, Special, CHOP, Hsc3p, baffled, EfW1, DmelCG4482, NON-PHOTOTROPHIC HYPOCOTYL, EK2-1, CD91, AI427929, chop, D2Wsu141e, D1Nds28, dmTAF1, 38kDa, Taf230, Perk, Growth arrest and DNA-damage-inducible protein GADD153, AL022860, sensitive, chaperonin ATPase activity, DmelCG3825, Growth arrest and DNA damage-inducible protein GADD153, non-chaperonin molecular chaperone ATPase activity, glycoprotein-specific chaperone activity, eIF-2gA, D2Ertd303e, MJC20.12, MASSUGU 1, Steroidogenesis-activator polypeptide, Hsce70, GRP-78, Globular, Enterprises, sensitivity, CCAAT|enhancer-binding protein homologous protein, Hsp-c3, l(2)br23, dhsc70, TAF250, Erk, ERK, SEZ-7, indole-3-acetic acid inducible 25, reactivity, Taf200, methods, dTAF[[II]]250, Unfolded Protein, MJC20_12, cell, experimental section, axis (CII), Taf1p, Events, Unfolded, Public Enterprises, indole-3-acetic acid inducible 21, CG18732, culm, Hsc70, indole-3-acetic acid inducible 23, Growth|differentiation factor 10, erk, dTAF250, Abstract, grp78, A2MR, MIF2, HSC70, Bone-inducing protein, Protein Folding, LRP1A, rll, DmERK-A, hypersensitivity reaction, TAF, Enterprise, Saeure, relational structural quality, DDIT-3, Controlled, TIR5, T1M15.130, data, Controlling, TAF[[II]]250, Chop10, Unfolded Protein Responses, CG4482, LRP, axis, l(2)35Bb, CT39192, Immunoglobulin heavy chain-binding protein, DmelCG1609, l(3)84Ab, BG:DS00004.13, CG3825, l(1)G0292, Cell, dTAF230, Concept, GCN2, Anniversaries, HSC-70, cervical axis, hsc70-3, Public, p230, Protein, TAF[[II]]250/230, feed, BIPOSTO, TFIID, TGFBR5, Vertebrate, protein complex assembly, Data Base, Taf[[II]]250, T1M15_130, hypersensitivity, C23, TRANSPORT INHIBITOR RESPONSE 5, AUXIN-RESPONSIVE TRANSCRIPTIONAL ACTIVATOR 7, hypersensitive, TAF[[II]]230, CG12559, Saeuren, Su(Raf)2B, cervical vertebra 2, dpERK1, phosphoric monoester hydrolase activity, CHOP10, TAF[II]250, EY2-2, GADD153, CG15268, CHOP-10, signalling, br3, AUXIN-REGULATED TRANSCRIPTIONAL ACTIVATOR 7, DmelCG17603, D-ERK, PPP1R67, signalling process, dpMAPK, luminal binding protein, l(1)G0407, Response, gadd34, NIP, Public., response, EIF2beta, CEBPZ, Protein Responses, TAF1Response, data, Unfolded., Vertebrate, Unfolded, Unfolded Protein, Logics, Unfolded Protein Responses, Protein Response, Protein Responses, ResponsesfalseDiedrichs2018 - A data-entrained computational model for testing the regulatory logic of the vertebrate unfolded protein response
A data-entrained computational model for
testing the regulatory logic of the vertebrate unfolded protein
response
This model is described in the article:
A data-entrained
computational model for testing the regulatory logic of the
vertebrate unfolded protein response.
Diedrichs DR, Gomez JA, Huang CS,
Rutkowski DT, Curtu R.
Mol. Biol. Cell 2018 Apr; :
mbcE17090565
Abstract:
The vertebrate unfolded protein response (UPR) is
characterized by multiple interacting nodes among its three
pathways, yet the logic underlying this regulatory complexity
is unclear. To begin to address this issue, we created a
computational model of the vertebrate UPR that was entrained
upon and then validated against experimental data. As part of
this validation, the model successfully predicted the
phenotypes of cells with lesions in UPR signaling, including a
surprising and previously unreported differential role for the
eIF2? phosphatase GADD34 in exacerbating severe stress but
ameliorating mild stress. We then used the model to test the
functional importance of a feed-forward circuit within the
PERK/CHOP axis, and of cross-regulatory control of BiP and CHOP
expression. We found that the wiring structure of the UPR
appears to balance the ability of the response to remain
sensitive to ER stress yet also to be rapidly deactivated by
improved protein folding conditions. This model should serve as
a valuable resource for further exploring the regulatory logic
of the UPR.
This model is hosted on
BioModels Database
and identified by:
MODEL1803300000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2018-05-242018-03-062018-03-30BIOMD0000000703R-HSA-381130R-HSA-38111929668363C21160MODEL1803300000BIOMD0000000703GO:0006986GO:0005783GO:0016310SO:0000234P18850Q99941P18848P35638O75807P05198P17861C21160Q9NZJ5O75460