The Homeodomain Iroquois Proteins Control Cell Cycle Progression and Regulate the Size of Developmental Fields: e1005463

During development, proper differentiation and final organ size rely on the control of territorial specification and cell proliferation. Although many regulators of these processes have been identified, how both are coordinated remains largely unknown. The homeodomain Iroquois/Irx proteins play a ke...

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Bibliographic Details
Published in:PLoS genetics 2015-08, Vol.11 (8)
Main Authors: Barrios, Natalia, González-Pérez, Esther, Hernández, Rosario, Campuzano, Sonsoles
Format: Article
Language:English
Subjects:
Apoptosis
Cancer
Cell cycle
Cell division
Cell growth
Drosophila iroquois
Experiments
Insects
Kinases
Localization
Proteins
Transcription factors
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Summary:During development, proper differentiation and final organ size rely on the control of territorial specification and cell proliferation. Although many regulators of these processes have been identified, how both are coordinated remains largely unknown. The homeodomain Iroquois/Irx proteins play a key, evolutionarily conserved, role in territorial specification. Here we show that in the imaginal discs, reduced function of Iroquois genes promotes cell proliferation by accelerating the G1 to S transition. Conversely, their increased expression causes cell-cycle arrest, down-regulating the activity of the Cyclin E/Cdk2 complex. We demonstrate that physical interaction of the Iroquois protein Caupolican with Cyclin E-containing protein complexes, through its IRO box and Cyclin-binding domains, underlies its activity in cell-cycle control. Thus, Drosophila Iroquois proteins are able to regulate cell-autonomously the growth of the territories they specify. Moreover, our results provide a molecular mechanism for a role of Iroquois/Irx genes as tumour suppressors.
ISSN:1553-7390
1553-7404
DOI:10.1371/journal.pgen.1005463