|Title||Gene regulation by MAPK substrate competition.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Kim, Y, Andreu, MJosé, Lim, B, Chung, K, Terayama, M, Jiménez, G, Berg, CA, Lu, H, Shvartsman, SY|
|Date Published||2011 Jun 14|
|Keywords||Animals, 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 Journal||Dev. Cell|