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.
Glavic
Alvaro
A
Millennium Nucleus Center for Genomics of the Cell, Department of Biology, Faculty of Sciences, University of Chile, Las Palmeras 3425, Santiago, Chile. alglavic@uchile.cl
Molnar
Cristina
C
Cotoras
Darko
D
de Celis
José F
JF
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009929:Organ Size; D010641:Phenotype; D021381:Protein Transport; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000166:cytology / Q000201:enzymology
C539705:Axud1 protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; D016203:CDC2 Protein Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila