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Antagonistic regulation of apoptosis and differentiation by the cut transcription factor represents a tumor-suppressing mechanism in drosophila

Zhai, Z., Ha, N., Papagiannouli, F, Hamacher-Brady, A., Brady, N., Sorge, S., Bezdan, D., Lohmann, I. (2012) Antagonistic regulation of apoptosis and differentiation by the cut transcription factor represents a tumor-suppressing mechanism in drosophila. PLoS Genetics, 8 (3). ISSN 1553-7390. (doi:10.1371/journal.pgen.1002582) (KAR id:78992)

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 oncogenic process.

Item Type: Article
DOI/Identification number: 10.1371/journal.pgen.1002582
Additional information: Unmapped bibliographic data: C7 - e1002582 [EPrints field already has value set] LA - English [Field not mapped to EPrints] J2 - PLoS Genet. [Field not mapped to EPrints] C2 - 22438831 [Field not mapped to EPrints] AD - CellNetworks-Cluster of Excellence, Centre for Organismal Studies (COS) Heidelberg, University of Heidelberg, Heidelberg, Germany [Field not mapped to EPrints] AD - German Cancer Research Center (DKFZ), Heidelberg, Germany [Field not mapped to EPrints] AD - Max Planck Institute for Developmental Biology, Tübingen, Germany [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints] M3 - Article [Field not mapped to EPrints]
Uncontrolled keywords: Cux1 protein, transcription factor, transcription factor Cut, unclassified drug, Cut protein, Drosophila, CUX1 protein, human, Drosophila protein, homeodomain protein, nuclear protein, reaper protein, Drosophila, repressor protein, transcription factor, animal cell, animal tissue, apoptosis, article, cancer cell, carcinogenesis, cell death, cell differentiation, cell lineage, controlled study, Drosophila, embryo, gene, gene expression regulation, human, human cell, nonhuman, protein function, reaper gene, stem cell, vertebrate, animal, cell strain HEK293, cell transformation, disease model, Drosophila melanogaster, genetics, metabolism, tumor suppressor gene, Vertebrata, Animals, Apoptosis, Cell Differentiation, Cell Lineage, Cell Transformation, Neoplastic, Disease Models, Animal, Drosophila melanogaster, Drosophila Proteins, Gene Expression Regulation, Developmental, Genes, Tumor Suppressor, HEK293 Cells, Homeodomain Proteins, Humans, Nuclear Proteins, Repressor Proteins, Transcription Factors
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Fani Papagiannouli
Date Deposited: 26 Nov 2019 14:31 UTC
Last Modified: 10 Jan 2024 18:18 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/78992 (The current URI for this page, for reference purposes)

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