A Toolkit for Developmental Biology:
Intrinsically Disordered Proteins,
Alternative Splicing, and Post-translational Modification
Keith Dunker
Center for Computational Biology and Bioinformatics
Department of Biochemistry and Molecular Biology
Indiana University Schools of Medicine and Informatics
Indianapolis, IN 46202, USA



Key developmental proteins use intrinsically disordered protein (IDP) regions to carry out crucial functions, typically to bind to and regulate the functions of their DNA/or protein partners. For all of these developmental proteins examined so far, these interactions are altered or modulated by both alternative splicing (AS) and by post-translational modification (PTM), both of which map to the IDP regions.  During development, both AS and PTMs in IDP regions have been shown to be tissue-specific.  Thus, both AS and PTMs “rewire” protein-protein and gene-regulatory networks and pathways in a tissue-specific manner.  Given these observations, we propose that IDP, AS, and PTM working in concert provide a toolkit that underlies (enables?) both the evolution of multicellular organisms and the developmental biology of individual multicellular organisms.



The p53 protein uses IDP regions to bind to > 100 protein partners, a few of which are shown here:
these interactions are altered by PTMs and AS!