Document Type
Article
Publication Date
2013
Keywords
Cancer Genomics, Cellular Signalling Networks, Gene Regulatory Networks, Systems Analysis
Digital Object Identifier (DOI)
https://doi.org/10.1038/srep02035
Abstract
IDPs, while structurally poor, are functionally rich by virtue of their flexibility and modularity. However, how mutations in IDPs elicit diseases, remain elusive. Herein, we have identified tumor suppressor PTEN as an intrinsically disordered protein (IDP) and elucidated the molecular principles by which its intrinsically disordered region (IDR) at the carboxyl-terminus (C-tail) executes its functions. Post-translational modifications, conserved eukaryotic linear motifs and molecular recognition features present in the C-tail IDR enhance PTEN's protein-protein interactions that are required for its myriad cellular functions. PTEN primary and secondary interactomes are also enriched in IDPs, most being cancer related, revealing that PTEN functions emanate from and are nucleated by the C-tail IDR, which form pliable network-hubs. Together, PTEN higher order functional networks operate via multiple IDP-IDP interactions facilitated by its C-tail IDR. Targeting PTEN IDR and its interaction hubs emerges as a new paradigm for treatment of PTEN related pathologies.
Rights Information
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Scientific Reports, v. 3, art. 2035
Scholar Commons Citation
Malaney, Prerna; Pathak, Ravi Ramesh; Xue, Bin; Uversky, Vladimir N.; and Davé, Vrushank, "Intrinsic Disorder in PTEN and Its Interactome Confers Structural Plasticity and Functional Versatility" (2013). Molecular Medicine Faculty Publications. 459.
https://digitalcommons.usf.edu/mme_facpub/459
Electronic Supplementary Material
