Gene Regulation by MAPK Substrate Competition

• Published in: Developmental cell Vol. 20; no. 6; pp. 880 - 887
• Main Authors: Kim, Yoosik, Andreu, María José, Lim, Bomyi, Chung, Kwanghun, Terayama, Mark, Jiménez, Gerardo, Berg, Celeste A., Lu, Hang, Shvartsman, Stanislav Y.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 14.06.2011; Cell Press
• Subjects: Animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Competition; Drosophila; Drosophila melanogaster - embryology; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; HMGB Proteins - metabolism; Homeodomain Proteins - metabolism; Immunoenzyme Techniques; In Situ Hybridization; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Models, Theoretical; Molecular and cellular biology; Phosphorylation; Repressor Proteins - metabolism; Signal Transduction; Trans-Activators - metabolism; Competition; Regulation(control); Gene; Enzyme; Transferases; Development; Mitogen-activated protein kinase
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2011.05.009

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. [Display omitted] ► MAPK substrates compete for access to MAPK in the early Drosophila embryo ► Anterior substrates promote Capicua action by blocking MAPK-dependent degradation ► Substrate competition explains gene expression patterns with complex AP/DV polarity