Gene regulation by MAPK substrate competition

Yoosik Kim, María José Andreu, Bomyi Lim, Kwanghun Chung, Mark Terayama, Gerardo Jiménez, Celeste A. Berg, Hang Lu, Stanislav Y. Shvartsman

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Abstract

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.

Original languageEnglish
Pages (from-to)880-887
Number of pages8
JournalDevelopmental Cell
Volume20
Issue number6
DOIs
Publication statusPublished - 2011 Jun 14

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Kim, Y., Andreu, M. J., Lim, B., Chung, K., Terayama, M., Jiménez, G., Berg, C. A., Lu, H., & Shvartsman, S. Y. (2011). Gene regulation by MAPK substrate competition. Developmental Cell, 20(6), 880-887. https://doi.org/10.1016/j.devcel.2011.05.009