Document Detail


The roles of intrinsic disorder in orchestrating the wnt-pathway.
MedLine Citation:
PMID:  22292947     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The canonical Wnt-pathway plays a number of crucial roles in the development of organism. Malfunctions of this pathway lead to various diseases including cancer. In the inactivated state, this pathway involves five proteins, Axin, CKI-α, GSK-3β, APC, and β-catenin. We analyzed these proteins by a number of computational tools, such as PONDR(r)VLXT, PONDR(r)VSL2, MoRF-II predictor and Hydrophobic Cluster Analysis (HCA) to show that each of the Wnt-pathway proteins contains several intrinsically disordered regions. Based on a comprehensive analysis of published data we conclude that these disordered regions facilitate protein-protein interactions, post-translational modifications, and signaling. The scaffold protein Axin and another large protein, APC, act as flexible concentrators in gathering together all other proteins involved in the Wnt-pathway, emphasizing the role of intrinsically disordered regions in orchestrating the complex protein-protein interactions. We further explore the intricate roles of highly disordered APC in regulation of β-catenin function. Intrinsically disordered APC helps the collection of β-catenin from cytoplasm, facilitates the b-catenin delivery to the binding sites on Axin, and controls the final detachment of β-catenin from Axin.
Authors:
B Xue; A K Dunker; V N Uversky
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of biomolecular structure & dynamics     Volume:  29     ISSN:  1538-0254     ISO Abbreviation:  J. Biomol. Struct. Dyn.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-02-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8404176     Medline TA:  J Biomol Struct Dyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  843-61     Citation Subset:  IM    
Affiliation:
Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA. vuversky@health.usf.edu.
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