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The Homeodomain Iroquois Proteins Control Cell Cycle Progression and Regulate the
Size of Developmental Fields
#MMPMID26305360
Barrios N
; González-Pérez E
; Hernández R
; Campuzano S
PLoS Genet
2015[Aug]; 11
(8
): e1005463
PMID26305360
show ga
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.
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