antagonistic regulation of apoptosis and differentiation by the cut transcription factor represents a tumor-suppressing mechanism in drosophila拮抗细胞凋亡和分化的调控转录因子代表了果蝇的肿瘤抑制机制.pdf

Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor- Suppressing Mechanism in Drosophila 1 1. 1. 2. 2. Zongzhao Zhai , Nati Ha , Fani Papagiannouli , Anne Hamacher-Brady , Nathan Brady , Sebastian 1 3 1 Sorge , Daniela Bezdan , Ingrid Lohmann * 1 CellNetworks–Cluster of Excellence, Centre for Organismal Studies (COS) Heidelberg, University of Heidelberg, Heidelberg, Germany, 2 German Cancer Research Center ¨ (DKFZ), Heidelberg, Germany, 3 Max Planck Institute for Developmental Biology, Tubingen, Germany Abstract Apoptosis is essential to prevent oncogenic transformation by triggering self-destruction of harmful cells, including those unable to differentiate. However, the mechanisms linking impaired cell differentiation and apoptosis during development and disease are not well understood. Here we report that the Drosophila transcription factor Cut coordinately controls differentiation and repression of apoptosis via direct regulation of the pro-apoptotic gene reaper. We also demonstrate that this regulatory circuit acts in diverse cell lineages to remove uncommitted precursor cells in status nascendi and thereby interferes with their potential to develop into cancer cells. Consistent with the role of Cut homologues in controlling cell death in vertebrates, we find repression of apoptosis regulators by Cux1 in human cancer cells. Finally, we present evidence that suggests that other lineage-restricted specification factors employ a similar mechanism to put the brakes on the