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Drosophila Axud1 is involved in the control of proliferation and displays pro-apoptotic activity

Drosophila Axud1 is involved in the control of proliferation and displays pro-apoptotic activity
Cell division rates and apoptosis sculpt the growing organs, and its regulation implements the developmental programmes that define organ size and shape. The balance between oncogenes and tumour suppressors modulate the cell cycle and the apoptotic machinery to achieve this goal, promoting and restricting proliferation or, in certain conditions, inducing the apoptotic programme. Analysis of human cancer cells with mutation in AXIN gene has uncovered the potential function of AXUD1 as a tumour suppressor. It has been described that Human AXUD1 is a nuclear protein. We find that a DAxud1-GFP fusion protein is localised to the nucleus during interphase, where it accumulates associated to the nuclear envelope, but becomes distributed in a diffused pattern in the nucleus of mitotic cells. We have analysed the function of the Drosophila AXUD1 homologue, and find that DAxud1 behaves as a tumour suppressor that regulates the proliferation rhythm of imaginal cells. Knocking down the activity of DAxud1 enhances the proliferation of these cells, causing in addition a reduction in cell size. Conversely, the increase in DAxud1 expression impedes cell cycle progression at mitosis through disturbance of Cdk1 activity, and induces the apoptosis of these cells in a JNK-dependent manner.
Embryology, Molecular Sequence Data, Apoptosis, Cell Cycle Proteins, CDC2 Protein Kinase, Animals, Drosophila Proteins, Wings, Animal, Amino Acid Sequence, Cell Proliferation, Cell Size, Tumor Suppressor Proteins, Cell Cycle, JNK Mitogen-Activated Protein Kinases, AXUD1 tumour suppressor, Gene Expression Regulation, Developmental, Organ Size, Protein Transport, Drosophila melanogaster, Phenotype, Protein Tyrosine Phosphatases, Developmental Biology, Subcellular Fractions
Embryology, Molecular Sequence Data, Apoptosis, Cell Cycle Proteins, CDC2 Protein Kinase, Animals, Drosophila Proteins, Wings, Animal, Amino Acid Sequence, Cell Proliferation, Cell Size, Tumor Suppressor Proteins, Cell Cycle, JNK Mitogen-Activated Protein Kinases, AXUD1 tumour suppressor, Gene Expression Regulation, Developmental, Organ Size, Protein Transport, Drosophila melanogaster, Phenotype, Protein Tyrosine Phosphatases, Developmental Biology, Subcellular Fractions
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