A Toolkit for Developmental Biology:
Intrinsically Disordered Proteins,
Alternative Splicing, and Post-translational Modification
(IDP-AS-PTM)
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

 

ABSTRACT:                                                                                                                                                                                                                         

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.

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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!
keith-dunker-figure-abstract2