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

Barrios N, González-Pérez E, Hernández R, Campuzano S - PLoS Genet. (2015)

Bottom Line: Conversely, their increased expression causes cell-cycle arrest, down-regulating the activity of the Cyclin E/Cdk2 complex.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Development and Differentiation, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Functional and physical interaction of Caup with the CycE/Cdk2 complex.Activity of the CycE/Cdk2 complex, monitored by MPM-2 staining (A, A’); cycE transcription (detected by in situ hybridization, B, C) and CycE accumulation (detected by immunostaining, D-F) in wing imaginal discs of the indicated genotypes. (G) Caup co-immunoprecipitates with CycE in S2 cells. Western blot of protein extracts from S2 cells expressing the indicated tagged proteins, immunoprecipitated with anti-HA or anti-V5 antibodies and probed with anti-HA. Black bars indicate position of the 100 KDa protein marker.
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pgen.1005463.g004: Functional and physical interaction of Caup with the CycE/Cdk2 complex.Activity of the CycE/Cdk2 complex, monitored by MPM-2 staining (A, A’); cycE transcription (detected by in situ hybridization, B, C) and CycE accumulation (detected by immunostaining, D-F) in wing imaginal discs of the indicated genotypes. (G) Caup co-immunoprecipitates with CycE in S2 cells. Western blot of protein extracts from S2 cells expressing the indicated tagged proteins, immunoprecipitated with anti-HA or anti-V5 antibodies and probed with anti-HA. Black bars indicate position of the 100 KDa protein marker.

Mentions: In Drosophila, the activity of the CycE/Cdk2 complex is required and sufficient for G1-S transition [32]. We examined the activity of this complex in cells that ectopically express caup by MPM-2 staining. This antibody recognizes a CycE/Cdk2 regulated protein complex that assembles into the histone locus body and is visualized as nuclear dots [40]. As shown in Fig 4A and 4A’, caup over-expressing cells of the posterior compartment (hhGal4 driver) displayed lower punctuated staining than control anterior cells indicating a decreased activity of the CycE/Cdk2 complex.


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

Barrios N, González-Pérez E, Hernández R, Campuzano S - PLoS Genet. (2015)

Functional and physical interaction of Caup with the CycE/Cdk2 complex.Activity of the CycE/Cdk2 complex, monitored by MPM-2 staining (A, A’); cycE transcription (detected by in situ hybridization, B, C) and CycE accumulation (detected by immunostaining, D-F) in wing imaginal discs of the indicated genotypes. (G) Caup co-immunoprecipitates with CycE in S2 cells. Western blot of protein extracts from S2 cells expressing the indicated tagged proteins, immunoprecipitated with anti-HA or anti-V5 antibodies and probed with anti-HA. Black bars indicate position of the 100 KDa protein marker.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549242&req=5

pgen.1005463.g004: Functional and physical interaction of Caup with the CycE/Cdk2 complex.Activity of the CycE/Cdk2 complex, monitored by MPM-2 staining (A, A’); cycE transcription (detected by in situ hybridization, B, C) and CycE accumulation (detected by immunostaining, D-F) in wing imaginal discs of the indicated genotypes. (G) Caup co-immunoprecipitates with CycE in S2 cells. Western blot of protein extracts from S2 cells expressing the indicated tagged proteins, immunoprecipitated with anti-HA or anti-V5 antibodies and probed with anti-HA. Black bars indicate position of the 100 KDa protein marker.
Mentions: In Drosophila, the activity of the CycE/Cdk2 complex is required and sufficient for G1-S transition [32]. We examined the activity of this complex in cells that ectopically express caup by MPM-2 staining. This antibody recognizes a CycE/Cdk2 regulated protein complex that assembles into the histone locus body and is visualized as nuclear dots [40]. As shown in Fig 4A and 4A’, caup over-expressing cells of the posterior compartment (hhGal4 driver) displayed lower punctuated staining than control anterior cells indicating a decreased activity of the CycE/Cdk2 complex.

Bottom Line: Conversely, their increased expression causes cell-cycle arrest, down-regulating the activity of the Cyclin E/Cdk2 complex.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Development and Differentiation, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus