TitleGene regulation by MAPK substrate competition.
Publication TypeJournal Article
Year of Publication2011
AuthorsKim, Y, Andreu, MJosé, Lim, B, Chung, K, Terayama, M, Jiménez, G, Berg, CA, Lu, H, Shvartsman, SY
JournalDev Cell
Date Published2011 Jun 14
KeywordsAnimals, Drosophila melanogaster, Drosophila Proteins, Embryo, Nonmammalian, Female, Gene Expression Regulation, Developmental, HMGB Proteins, Homeodomain Proteins, Immunoenzyme Techniques, In Situ Hybridization, Mitogen-Activated Protein Kinases, Models, Theoretical, Phosphorylation, Repressor Proteins, Signal Transduction, Trans-Activators

Developing tissues are patterned by coordinated activities of signaling systems, which can be integrated by a regulatory region of a gene that binds multiple transcription factors or by a transcription factor that is modified by multiple enzymes. Based on a combination of genetic and imaging experiments in the early Drosophila embryo, we describe a signal integration mechanism that cannot be reduced to a single gene regulatory element or a single transcription factor. This mechanism relies on an enzymatic network formed by mitogen-activated protein kinase (MAPK) and its substrates. Specifically, anteriorly localized MAPK substrates, such as Bicoid, antagonize MAPK-dependent downregulation of Capicua, a repressor that is involved in gene regulation along the dorsoventral axis of the embryo. MAPK substrate competition provides a basis for ternary interaction of the anterior, dorsoventral, and terminal patterning systems. A mathematical model of this interaction can explain gene expression patterns with both anteroposterior and dorsoventral polarities.

Alternate JournalDev. Cell