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The bHLH Factors Extramacrochaetae and Daughterless Control Cell Cycle in Imaginal Discs through the Transcriptional Regulation of the Phosphatase


Precise control of cell proliferation is critical for normal development and tissue homeostasis. Members of the inhibitor of differentiation (Id) family of helix-loop-helix (HLH) proteins are key regulators that coordinate the balance between cell division and differentiation. These proteins exert this function in part by combining with ubiquitously expressed bHLH transcription factors (E proteins), preventing these transcription factors from forming functional hetero- or homodimeric DNA binding complexes. Deregulation of the activity of Id proteins frequently leads to tumour formation. The Daughterless (Da) and Extramacrochaetae (Emc) proteins are the only members of the E and Id families in Drosophila, yet their role in the control of cell proliferation has not been determined. In this study, we show that the elimination of emc or the ectopic expression of da arrests cells in the G2 phase of the cell cycle. Moreover, we demonstrate that emc controls cell proliferation via Da, which acts as a transcriptional repressor of the Cdc25 phosphatase string. These results provide an important insight into the mechanisms through which Id and E protein interactions control cell cycle progression and therefore how the disruption of the function of Id proteins can induce oncogenic transformation.


Vyšlo v časopise: The bHLH Factors Extramacrochaetae and Daughterless Control Cell Cycle in Imaginal Discs through the Transcriptional Regulation of the Phosphatase. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004233
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004233

Souhrn

Precise control of cell proliferation is critical for normal development and tissue homeostasis. Members of the inhibitor of differentiation (Id) family of helix-loop-helix (HLH) proteins are key regulators that coordinate the balance between cell division and differentiation. These proteins exert this function in part by combining with ubiquitously expressed bHLH transcription factors (E proteins), preventing these transcription factors from forming functional hetero- or homodimeric DNA binding complexes. Deregulation of the activity of Id proteins frequently leads to tumour formation. The Daughterless (Da) and Extramacrochaetae (Emc) proteins are the only members of the E and Id families in Drosophila, yet their role in the control of cell proliferation has not been determined. In this study, we show that the elimination of emc or the ectopic expression of da arrests cells in the G2 phase of the cell cycle. Moreover, we demonstrate that emc controls cell proliferation via Da, which acts as a transcriptional repressor of the Cdc25 phosphatase string. These results provide an important insight into the mechanisms through which Id and E protein interactions control cell cycle progression and therefore how the disruption of the function of Id proteins can induce oncogenic transformation.


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