Intrinsically disordered proteins link alternative splicing and post-translational modifications to complex cell signaling and regulation

dc.contributor.authorZhou, Jianhong
dc.contributor.authorZhao, Suwen
dc.contributor.authorDunker, A. Keith
dc.contributor.departmentBiochemistry and Molecular Biology, School of Medicineen_US
dc.date.accessioned2018-04-12T15:51:53Z
dc.date.available2018-04-12T15:51:53Z
dc.date.issued2018
dc.description.abstractIntrinsically disordered proteins and regions (IDPs and IDRs) lack well-defined tertiary structures, yet carry out various important cellular functions, especially those associated with cell signaling and regulation. In eukaryotes, IDPs and IDRs contain the preferred loci for both alternative splicing (AS) and many post-translational modifications (PTMs). Furthermore, AS and/or PTMs at these loci generally alter the signaling outcomes associated with these IDPs or IDRs, where the functional cooperation of these three features is named the IDP-AS-PTM toolkit. However, the prevalence of such functional modulations remains unknown. Also, the signal-altering mechanisms by which AS, and PTMs modulate function and the extent to which AS and PTMs collaborate in their signaling modulations have not been well defined for particular protein examples. Here we focus on three important signaling and regulatory IDR-containing protein families in humans, namely G-protein coupled receptors (GPCRs), which are transmembrane proteins, the nuclear factors of activated T-cells (NFATs), which are transcription factors (TFs), and the Src family kinases (SFKs), which are signaling enzymes. The goal here is to determine how AS and PTMs individually alter the outcomes of the signaling carried out by the various IDRs and to determine whether AS and PTMs work together to bring about differential cellular responses. We also present data indicating that a wide range of other signaling IDPs or IDRs undergo both AS- and PTM-based modifications, suggesting that they, too, likely take advantage of signal outcome modulations that result from collaboration between these two events. Hence, we propose that the widespread cooperation of IDPs, AS and/or PTMs provides a IDP-AS-PTM toolkit and substantially contributes to the vast complexity of eukaryotic cell signaling systems.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationZhou, J., Zhao, S., & Keith Dunker, A. (2018). Intrinsically disordered proteins link alternative splicing and post-translational modifications to complex cell signaling and regulation. Journal of Molecular Biology. https://doi.org/10.1016/j.jmb.2018.03.028en_US
dc.identifier.urihttps://hdl.handle.net/1805/15852
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.jmb.2018.03.028en_US
dc.relation.journalJournal of Molecular Biologyen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectintrinsic disorderen_US
dc.subjectalternative splicingen_US
dc.subjectpost-translational modificationen_US
dc.titleIntrinsically disordered proteins link alternative splicing and post-translational modifications to complex cell signaling and regulationen_US
dc.typeArticleen_US
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