Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells
Abstract
In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β—catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β—catenin, serine/threonine kinases, and other proteins. The kinases CK1α and GSK–3β, which are recruited by Axin, mediate phosphorylation of β—catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β—catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a rule-based computational model, we investigated the regulation of β—catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. In this paper, we find that the phosphorylated truncated form of APC can outcompete Axin for binding to β—catenin, provided that Axin is limiting, and thereby sequester β—catenin away from Axin and the Axin-recruited kinases CK1α and GSK–3β. Full-length APC also competes with Axin for binding to β—catenin; however, full-lengthmore »
- Authors:
-
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group. Theoretical Division. Center for Nonlinear Studies
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group. Theoretical Division. Center for Nonlinear Studies; Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Biology; Translational Genomics Research Inst., Phoenix, AZ (United States). Clinical Translational Research Division
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE; National Inst. of Health (NIH) (United States)
- OSTI Identifier:
- 1321723
- Report Number(s):
- LA-UR-13-20383
Journal ID: ISSN 1553-7358
- Grant/Contract Number:
- AC52-06NA25396; R01GM076570; P50GM085273
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS Computational Biology (Online)
- Additional Journal Information:
- Journal Name: PLoS Computational Biology (Online); Journal Volume: 9; Journal Issue: 9; Journal ID: ISSN 1553-7358
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; biological science; antigen-presenting cells; phosphorylation; SW480 cells; protein interactions; cell binding; chemical dissociation; transfection; colorectal cancer
Citation Formats
Barua, Dipak, and Hlavacek, William S. Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells. United States: N. p., 2013.
Web. doi:10.1371/journal.pcbi.1003217.
Barua, Dipak, & Hlavacek, William S. Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells. United States. https://doi.org/10.1371/journal.pcbi.1003217
Barua, Dipak, and Hlavacek, William S. Thu .
"Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells". United States. https://doi.org/10.1371/journal.pcbi.1003217. https://www.osti.gov/servlets/purl/1321723.
@article{osti_1321723,
title = {Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells},
author = {Barua, Dipak and Hlavacek, William S.},
abstractNote = {In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β—catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β—catenin, serine/threonine kinases, and other proteins. The kinases CK1α and GSK–3β, which are recruited by Axin, mediate phosphorylation of β—catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β—catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a rule-based computational model, we investigated the regulation of β—catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. In this paper, we find that the phosphorylated truncated form of APC can outcompete Axin for binding to β—catenin, provided that Axin is limiting, and thereby sequester β—catenin away from Axin and the Axin-recruited kinases CK1α and GSK–3β. Full-length APC also competes with Axin for binding to β—catenin; however, full-length APC is able, through its SAMP repeats, which bind Axin and which are missing in truncated oncogenic forms of APC, to bring β—catenin into indirect association with Axin and Axin-recruited kinases. Because our model indicates that the positive effects of truncated APC on β—catenin levels depend on phosphorylation of APC, at the first 20-amino acid repeat, and because phosphorylation of this site is mediated by CK1ϵ, we suggest that CK1ϵ is a potential target for therapeutic intervention in colorectal cancer. Finally, specific inhibition of CK1ϵ is predicted to limit binding of β—catenin to truncated APC and thereby to reverse the effect of APC truncation.},
doi = {10.1371/journal.pcbi.1003217},
journal = {PLoS Computational Biology (Online)},
number = 9,
volume = 9,
place = {United States},
year = {Thu Sep 26 00:00:00 EDT 2013},
month = {Thu Sep 26 00:00:00 EDT 2013}
}
Web of Science
Works referenced in this record:
The Third 20 Amino Acid Repeat Is the Tightest Binding Site of APC for β-Catenin
journal, June 2006
- Liu, Jing; Xing, Yi; Hinds, Thomas R.
- Journal of Molecular Biology, Vol. 360, Issue 1
Scaffold-mediated Nucleation of Protein Signaling Complexes: Elementary Principles
text, January 2011
- Yang, Jin; Hlavacek, William S.
- arXiv
β-Catenin destruction complex: insights and questions from a structural perspective
journal, December 2006
- Kimelman, D.; Xu, W.
- Oncogene, Vol. 25, Issue 57
Regulation of S33/S37 phosphorylated β-catenin in normal and transformed cells
journal, July 2002
- Sadot, Einat; Conacci-Sorrell, Maralice; Zhurinsky, Jacob
- Journal of Cell Science, Vol. 115, Issue 13
GSK-3β-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by β-catenin and protein phosphatase 2A complexed with Axin
journal, January 2000
- Ikeda, Satoshi; Kishida, Michiko; Matsuura, Yoshiharu
- Oncogene, Vol. 19, Issue 4
Wnt signaling and colon tumorigenesis — A view from the periphery
journal, November 2011
- Burgess, Antony W.; Faux, Maree C.; Layton, Meredith J.
- Experimental Cell Research, Vol. 317, Issue 19
The -Catenin Destruction Complex
journal, November 2012
- Stamos, J. L.; Weis, W. I.
- Cold Spring Harbor Perspectives in Biology, Vol. 5, Issue 1
Axin-independent phosphorylation of APC controls β-catenin signaling via cytoplasmic retention of β-catenin
journal, May 2007
- Seo, Eunjeong; Jho, Eek-hoon
- Biochemical and Biophysical Research Communications, Vol. 357, Issue 1
The APC gene product in normal and tumor cells.
journal, April 1993
- Smith, K. J.; Johnson, K. A.; Bryan, T. M.
- Proceedings of the National Academy of Sciences, Vol. 90, Issue 7
Armadillo Coactivates Transcription Driven by the Product of the Drosophila Segment Polarity Gene dTCF
journal, March 1997
- van de Wetering, Marc; Cavallo, Robert; Dooijes, Dennis
- Cell, Vol. 88, Issue 6
The complexity of complexes in signal transduction
journal, December 2003
- Hlavacek, William S.; Faeder, James R.; Blinov, Michael L.
- Biotechnology and Bioengineering, Vol. 84, Issue 7
Hot spots in β-catenin for interactions with LEF-1, conductin and APC
journal, September 2000
- Birchmeier, Walter; von Kries, Jens Peter; Winbeck, Georgia
- Nature Structural Biology, Vol. 7, Issue 9, p. 800-807
β-catenin is a target for the ubiquitin–proteasome pathway
journal, July 1997
- Aberle, Hermann; Bauer, Andreas; Stappert, Jörg
- The EMBO Journal, Vol. 16, Issue 13
RuleBender: a visual interface for rule-based modeling
journal, April 2011
- Xu, Wen; Smith, Adam M.; Faeder, James R.
- Bioinformatics, Vol. 27, Issue 12
Innovations of the Rule-Based Modeling Approach
book, January 2013
- Chylek, Lily A.; Stites, Edward C.; Posner, Richard G.
- Systems Biology
The influence of polyvalency on the binding properties of antibodies
journal, March 1972
- Crothers, Donald M.; Metzger, Henry
- Immunochemistry, Vol. 9, Issue 3
Modular Peptide Recognition Domains in Eukaryotic Signaling
journal, June 1997
- Kuriyan, John; Cowburn, David
- Annual Review of Biophysics and Biomolecular Structure, Vol. 26, Issue 1
Selective Inhibition of Casein Kinase 1ϵ Minimally Alters Circadian Clock Period
journal, May 2009
- Walton, Kevin M.; Fisher, Katherine; Rubitski, David
- Journal of Pharmacology and Experimental Therapeutics, Vol. 330, Issue 2
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex
journal, February 2003
- Dajani, R.
- The EMBO Journal, Vol. 22, Issue 3
Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta -catenin and promotes GSK-3beta -dependent phosphorylation of beta -catenin
journal, March 1998
- Ikeda, S.
- The EMBO Journal, Vol. 17, Issue 5
The Pfam protein families database
journal, November 2009
- Finn, Robert D.; Mistry, Jaina; Tate, John
- Nucleic Acids Research, Vol. 38, Issue suppl_1
E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.
journal, December 1994
- Hülsken, J.; Birchmeier, W.; Behrens, J.
- Journal of Cell Biology, Vol. 127, Issue 6
The Roles of APC and Axin Derived from Experimental and Theoretical Analysis of the Wnt Pathway
journal, October 2003
- Lee, Ethan; Salic, Adrian; Krüger, Roland
- PLoS Biology, Vol. 1, Issue 1
SUNDIALS: Suite of nonlinear and differential/algebraic equation solvers
journal, September 2005
- Hindmarsh, Alan C.; Brown, Peter N.; Grant, Keith E.
- ACM Transactions on Mathematical Software, Vol. 31, Issue 3
GSK3 takes centre stage more than 20 years after its discovery
journal, September 2001
- Frame, Sheelagh; Cohen, Philip
- Biochemical Journal, Vol. 359, Issue 1
IC261, a specific inhibitor of the protein kinases casein kinase 1-delta and -epsilon, triggers the mitotic checkpoint and induces p53-dependent postmitotic effects
journal, November 2000
- Behrend, L.; Milne, D. M.; Stöter, M.
- Oncogene, Vol. 19, Issue 47
Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3β
journal, May 1998
- Hart, Matthew J.; de los Santos, Rico; Albert, Iris N.
- Current Biology, Vol. 8, Issue 10
Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex
journal, November 2001
- Eklof Spink, K.
- The EMBO Journal, Vol. 20, Issue 22
XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos
journal, August 1996
- Molenaar, Miranda; van de Wetering, Marc; Oosterwegel, Mariette
- Cell, Vol. 86, Issue 3
Rule-based modeling of biochemical networks
journal, January 2005
- Faeder, James R.; Blinov, Michael L.; Goldstein, Byron
- Complexity, Vol. 10, Issue 4
Wnt Signaling in Oncogenesis and Embryogenesis--a Look Outside the Nucleus
journal, March 2000
- Peifer, M.
- Science, Vol. 287, Issue 5458
Restoration of full-length adenomatous polyposis coli (APC) protein in a colon cancer cell line enhances cell adhesion
journal, December 2003
- Faux, M. C.
- Journal of Cell Science, Vol. 117, Issue 3
BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains
journal, June 2004
- Blinov, M. L.; Faeder, J. R.; Goldstein, B.
- Bioinformatics, Vol. 20, Issue 17
Infrastructure for the life sciences: design and implementation of the UniProt website
journal, January 2009
- Jain, Eric; Bairoch, Amos; Duvaud, Severine
- BMC Bioinformatics, Vol. 10, Issue 1
Recruitment of adenomatous polyposis coli and β-catenin to axin-puncta
journal, June 2008
- Faux, M. C.; Coates, J. L.; Catimel, B.
- Oncogene, Vol. 27, Issue 44
Wnt/Wingless signaling through β-catenin requires the function of both LRP/Arrow and frizzled classes of receptors
journal, January 2003
- Schweizer, Liang; Varmus, Harold
- BMC Cell Biology, Vol. 4, Issue 1
Structural basis of the Axin–adenomatous polyposis coli interaction
journal, May 2000
- Spink, Katharine Eklof; Polakis, Paul; Weis, William I.
- The EMBO Journal, Vol. 19, Issue 10
Intramolecular Reaction in Polycondensations. I. The Theory of Linear Systems
journal, December 1950
- Jacobson, Homer; Stockmayer, Walter H.
- The Journal of Chemical Physics, Vol. 18, Issue 12
Crystal Structure of a β-Catenin/APC Complex Reveals a Critical Role for APC Phosphorylation in APC Function
journal, August 2004
- Xing, Yi; Clements, Wilson K.; Le Trong, Isolde
- Molecular Cell, Vol. 15, Issue 4
The Pfam protein families database
journal, November 2009
- Finn, Robert D.; Mistry, Jaina; Tate, John
- Nucleic Acids Research, Vol. 38, Issue suppl_1
Wnt/β-Catenin Signaling in Development and Disease
journal, November 2006
- Clevers, Hans
- Cell, Vol. 127, Issue 3
β-catenin is a target for the ubiquitin–proteasome pathway
journal, July 1997
- Aberle, Hermann; Bauer, Andreas; Stappert, Jörg
- The EMBO Journal, Vol. 16, Issue 13
A Comprehensive Mathematical Model for Three-Body Binding Equilibria
journal, April 2013
- Douglass, Eugene F.; Miller, Chad J.; Sparer, Gerson
- Journal of the American Chemical Society, Vol. 135, Issue 16
Dynamic recruitment of axin by Dishevelled protein assemblies
journal, July 2007
- Schwarz-Romond, T.; Metcalfe, C.; Bienz, M.
- Journal of Cell Science, Vol. 120, Issue 14
Differential Mechanisms of LEF/TCF Family-Dependent Transcriptional Activation by β-Catenin and Plakoglobin
journal, June 2000
- Zhurinsky, Jacob; Shtutman, Michael; Ben-Ze'ev, Avri
- Molecular and Cellular Biology, Vol. 20, Issue 12
Kinetic Responses of -Catenin Specify the Sites of Wnt Control
journal, November 2012
- Hernandez, A. R.; Klein, A. M.; Kirschner, M. W.
- Science, Vol. 338, Issue 6112
Stabilization of beta -Catenin by Genetic Defects in Melanoma Cell Lines
journal, March 1997
- Rubinfeld, B.
- Science, Vol. 275, Issue 5307
Dynamic recruitment of axin by Dishevelled protein assemblies
journal, July 2007
- Schwarz-Romond, T.; Metcalfe, C.; Bienz, M.
- Journal of Cell Science, Vol. 120, Issue 14
Wnt signaling and colon tumorigenesis — A view from the periphery
journal, November 2011
- Burgess, Antony W.; Faux, Maree C.; Layton, Meredith J.
- Experimental Cell Research, Vol. 317, Issue 19
GSK3: a multifaceted kinase in Wnt signaling
journal, March 2010
- Wu, Dianqing; Pan, Weijun
- Trends in Biochemical Sciences, Vol. 35, Issue 3
The subcellular destinations of apc proteins
journal, May 2002
- Bienz, Mariann
- Nature Reviews Molecular Cell Biology, Vol. 3, Issue 5
Functional Domains of Axin: IMPORTANCE OF THE C TERMINUS AS AN OLIGOMERIZATION DOMAIN
journal, May 1999
- Sakanaka, Chie; Williams, Lewis T.
- Journal of Biological Chemistry, Vol. 274, Issue 20
Wnt Signaling through Inhibition of β-Catenin Degradation in an Intact Axin1 Complex
journal, June 2012
- Li, Vivian S. W.; Ng, Ser Sue; Boersema, Paul J.
- Cell, Vol. 149, Issue 6
Nuclear-cytoplasmic shuttling of APC regulates β-catenin subcellular localization and turnover
journal, August 2000
- Henderson, Beric R.
- Nature Cell Biology, Vol. 2, Issue 9
Crystal Structure of a β-Catenin/APC Complex Reveals a Critical Role for APC Phosphorylation in APC Function
journal, August 2004
- Xing, Yi; Clements, Wilson K.; Le Trong, Isolde
- Molecular Cell, Vol. 15, Issue 4
β-Catenin destruction complex: insights and questions from a structural perspective
journal, December 2006
- Kimelman, D.; Xu, W.
- Oncogene, Vol. 25, Issue 57
Universally Sloppy Parameter Sensitivities in Systems Biology Models
journal, January 2007
- Gutenkunst, Ryan N.; Waterfall, Joshua J.; Casey, Fergal P.
- PLoS Computational Biology, Vol. 3, Issue 10
The influence of polyvalency on the binding properties of antibodies
journal, March 1972
- Crothers, Donald M.; Metzger, Henry
- Immunochemistry, Vol. 9, Issue 3
Wnt signals across the plasma membrane to activate the -catenin pathway by forming oligomers containing its receptors, Frizzled and LRP
journal, October 2004
- Cong, F.
- Development, Vol. 131, Issue 20
Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.
journal, March 1995
- Munemitsu, S.; Albert, I.; Souza, B.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 7
Alternative modes of binding of proteins with tandem SH2 domains
journal, January 2000
- O'Brien, Ronan; Renzoni, Debora; Waterfield, Michael D.
- Protein Science, Vol. 9, Issue 3
Crystal structure of a -catenin/Axin complex suggests a mechanism for the -catenin destruction complex
journal, November 2003
- Xing, Y.
- Genes & Development, Vol. 17, Issue 22
A new face and new challenges for Online Mendelian Inheritance in Man (OMIM®)
journal, April 2011
- Amberger, Joanna; Bocchini, Carol; Hamosh, Ada
- Human Mutation, Vol. 32, Issue 5
Three decades of Wnts: a personal perspective on how a scientific field developed: Three decades of Wnts: a personal perspective
journal, May 2012
- Nusse, Roel; Varmus, Harold
- The EMBO Journal, Vol. 31, Issue 12
Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
journal, March 2002
- Liu, Chunming; Li, Yiming; Semenov, Mikhail
- Cell, Vol. 108, Issue 6
An Inhibitor of Casein Kinase Iϵ Induces Phase Delays in Circadian Rhythms under Free-Running and Entrained Conditions
journal, May 2007
- Badura, Lori; Swanson, Terri; Adamowicz, Wendy
- Journal of Pharmacology and Experimental Therapeutics, Vol. 322, Issue 2
Molecular Basis of Colorectal Cancer
journal, December 2009
- Markowitz, Sanford D.; Bertagnolli, Monica M.
- New England Journal of Medicine, Vol. 361, Issue 25
CVODE, A Stiff/Nonstiff ODE Solver in C
journal, January 1996
- Cohen, Scott D.; Hindmarsh, Alan C.; Dubois, Paul F.
- Computers in Physics, Vol. 10, Issue 2
Regulation of Glycogen Synthase Kinase 3β and Downstream Wnt Signaling by Axin
journal, October 1999
- Hedgepeth, Chester M.; Deardorff, Matthew A.; Rankin, Kathleen
- Molecular and Cellular Biology, Vol. 19, Issue 10
Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex
journal, November 2001
- Eklof Spink, K.
- The EMBO Journal, Vol. 20, Issue 22
Axin, a Negative Regulator of the Wnt Signaling Pathway, Directly Interacts with Adenomatous Polyposis Coli and Regulates the Stabilization of β-Catenin
journal, May 1998
- Kishida, Shosei; Yamamoto, Hideki; Ikeda, Satoshi
- Journal of Biological Chemistry, Vol. 273, Issue 18
A Role of Dishevelled in Relocating Axin to the Plasma Membrane during Wingless Signaling
journal, May 2003
- Cliffe, Adam; Hamada, Fumihiko; Bienz, Mariann
- Current Biology, Vol. 13, Issue 11
Functional interaction of β-catenin with the transcription factor LEF-1
journal, August 1996
- Behrens, Jürgen; von Kries, Jens P.; Kühl, Michael
- Nature, Vol. 382, Issue 6592
Modular Peptide Recognition Domains in Eukaryotic Signaling
journal, June 1997
- Kuriyan, John; Cowburn, David
- Annual Review of Biophysics and Biomolecular Structure, Vol. 26, Issue 1
Rules for Modeling Signal-Transduction Systems
journal, July 2006
- Hlavacek, W. S.; Faeder, J. R.; Blinov, M. L.
- Science Signaling, Vol. 2006, Issue 344
Intramolecular Reaction in Polycondensations. I. The Theory of Linear Systems
journal, December 1950
- Jacobson, Homer; Stockmayer, Walter H.
- The Journal of Chemical Physics, Vol. 18, Issue 12
Functional Interaction of an Axin Homolog, Conductin, with -Catenin, APC, and GSK3
journal, April 1998
- Behrens, J.
- Science, Vol. 280, Issue 5363
Wnt signals across the plasma membrane to activate the -catenin pathway by forming oligomers containing its receptors, Frizzled and LRP
journal, October 2004
- Cong, F.
- Development, Vol. 131, Issue 20
Computational Models of Tandem Src Homology 2 Domain Interactions and Application to Phosphoinositide 3-Kinase
journal, January 2008
- Barua, Dipak; Faeder, James R.; Haugh, Jason M.
- Journal of Biological Chemistry, Vol. 283, Issue 12
A new face and new challenges for Online Mendelian Inheritance in Man (OMIM®)
journal, April 2011
- Amberger, Joanna; Bocchini, Carol; Hamosh, Ada
- Human Mutation, Vol. 32, Issue 5
Recruitment of adenomatous polyposis coli and β-catenin to axin-puncta
journal, June 2008
- Faux, M. C.; Coates, J. L.; Catimel, B.
- Oncogene, Vol. 27, Issue 44
Wnt Signalling Pathway Parameters for Mammalian Cells
journal, February 2012
- Tan, Chin Wee; Gardiner, Bruce S.; Hirokawa, Yumiko
- PLoS ONE, Vol. 7, Issue 2
Guidelines for visualizing and annotating rule-based models
journal, January 2011
- Chylek, Lily A.; Hu, Bin; Blinov, Michael L.
- Molecular BioSystems, Vol. 7, Issue 10
Scaffold-mediated nucleation of protein signaling complexes: Elementary principles
journal, August 2011
- Yang, Jin; Hlavacek, William S.
- Mathematical Biosciences, Vol. 232, Issue 2
Structural basis of the Axin–adenomatous polyposis coli interaction
journal, May 2000
- Spink, Katharine Eklof; Polakis, Paul; Weis, William I.
- The EMBO Journal, Vol. 19, Issue 10
Crystal Structure of a β-Catenin/Tcf Complex
journal, December 2000
- Graham, Thomas A.; Weaver, Carole; Mao, Feng
- Cell, Vol. 103, Issue 6
The APC tumour suppressor has a nuclear export function
journal, August 2000
- Rosin-Arbesfeld, Rina; Townsley, Fiona; Bienz, Mariann
- Nature, Vol. 406, Issue 6799
Mechanism of Phosphorylation-Dependent Binding of APC to β-Catenin and Its Role in β-Catenin Degradation
journal, August 2004
- Ha, Nam-Chul; Tonozuka, Takashi; Stamos, Jennifer L.
- Molecular Cell, Vol. 15, Issue 4
BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains
journal, June 2004
- Blinov, M. L.; Faeder, J. R.; Goldstein, B.
- Bioinformatics, Vol. 20, Issue 17
Basic region of residues 228-231 of protein kinase CK1? is involved in its interaction with axin: Binding to axin does not affect the kinase activity
journal, January 2005
- Sobrado, Pablo; Jedlicki, Ana; Bustos, Victor H.
- Journal of Cellular Biochemistry, Vol. 94, Issue 2
Infrastructure for the life sciences: design and implementation of the UniProt website
journal, January 2009
- Jain, Eric; Bairoch, Amos; Duvaud, Severine
- BMC Bioinformatics, Vol. 10, Issue 1
The subcellular destinations of apc proteins
journal, May 2002
- Bienz, Mariann
- Nature Reviews Molecular Cell Biology, Vol. 3, Issue 5
Adenomatous Polyposis Coli (APC) Differentially Regulates β-Catenin Phosphorylation and Ubiquitination in Colon Cancer Cells
journal, April 2006
- Yang, Jun; Zhang, Wen; Evans, Paul M.
- Journal of Biological Chemistry, Vol. 281, Issue 26
Axin-dependent Phosphorylation of the Adenomatous Polyposis Coli Protein Mediated by Casein Kinase 1ε
journal, August 2001
- Rubinfeld, Bonnee; Tice, David A.; Polakis, Paul
- Journal of Biological Chemistry, Vol. 276, Issue 42
Rules for Modeling Signal-Transduction Systems
journal, July 2006
- Hlavacek, W. S.; Faeder, J. R.; Blinov, M. L.
- Science Signaling, Vol. 2006, Issue 344
Regulation of S33/S37 phosphorylated β-catenin in normal and transformed cells
journal, July 2002
- Sadot, Einat; Conacci-Sorrell, Maralice; Zhurinsky, Jacob
- Journal of Cell Science, Vol. 115, Issue 13
Works referencing / citing this record:
Mathematical modelling suggests a differential impact of β-transducin repeat-containing protein paralogues on Wnt/β-catenin signalling dynamics
journal, February 2015
- Benary, Uwe; Kofahl, Bente; Hecht, Andreas
- The FEBS Journal, Vol. 282, Issue 6
Differences in sensitivity to EGFR inhibitors could be explained by described biochemical differences between oncogenic Ras mutants
posted_content, May 2014
- Stites, Edward C.
- bioRxiv
An Interaction Library for the FcεRI Signaling Network
journal, April 2014
- Chylek, Lily A.; Holowka, David A.; Baird, Barbara A.
- Frontiers in Immunology, Vol. 5
Forward and Backward Bisimulations for Chemical Reaction Networks
text, January 2015
- Cardelli, Luca; Tribastone, Mirco; Tschaikowski, Max
- Schloss Dagstuhl - Leibniz-Zentrum fuer Informatik GmbH, Wadern/Saarbruecken, Germany
Multicellular Models Bridging Intracellular Signaling and Gene Transcription to Population Dynamics
journal, November 2018
- Islam, Mohammad; Roy, Satyaki; Das, Sajal
- Processes, Vol. 6, Issue 11
Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer
journal, June 2018
- Choi, Yuri; Kwon, Chae Hwa; Lee, Seon Jin
- British Journal of Cancer, Vol. 119, Issue 2
Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer
journal, June 2018
- Choi, Yuri; Kwon, Chae Hwa; Lee, Seon Jin
- British Journal of Cancer, Vol. 119, Issue 2
Extracellular inhibitors can attenuate tumorigenic Wnt pathway activity in adenomatous polyposis coli mutants: Predictions of a validated mathematical model
journal, July 2017
- Hochman, Gili; Halevi-Tobias, Karin; Kogan, Yuri
- PLOS ONE, Vol. 12, Issue 7
Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment
journal, January 2019
- Norton, Kerri-Ann; Gong, Chang; Jamalian, Samira
- Processes, Vol. 7, Issue 1
Timescale Separation of Positive and Negative Signaling Creates History-Dependent Responses to IgE Receptor Stimulation
journal, November 2017
- Harmon, Brooke; Chylek, Lily A.; Liu, Yanli
- Scientific Reports, Vol. 7, Issue 1
Multiscale Agent-Based and Hybrid Modeling of the Tumor Immune Microenvironment
journal, January 2019
- Norton, Kerri-Ann; Gong, Chang; Jamalian, Samira
- Processes, Vol. 7, Issue 1