Academic Journal
The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models
| Title: | The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models |
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| Authors: | Carmen Vicente, Rocco Stirparo, Sofie Demeyer, Charles E. de Bock, Olga Gielen, Mardelle Atkins, Jiekun Yan, Georg Halder, Bassem A. Hassan, Jan Cools |
| Source: | Journal of Hematology & Oncology, Vol 11, Iss 1, Pp 1-16 (2018) |
| Publisher Information: | BMC, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Diseases of the blood and blood-forming organs LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | CCR4-NOT, Leukemia, mRNA stability, Tumor suppressor, Drosophila melanogaster, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Abstract Background The CNOT3 protein is a subunit of the CCR4-NOT complex, which is involved in mRNA degradation. We recently identified CNOT3 loss-of-function mutations in patients with T-cell acute lymphoblastic leukemia (T-ALL). Methods Here, we use different Drosophila melanogaster eye cancer models to study the potential tumor suppressor function of Not3, the CNOT3 orthologue, and other members of the CCR4-NOT complex. Results Our data show that knockdown of Not3, the structural components Not1/Not2, and the deadenylases twin/Pop2 all result in increased tumor formation. In addition, overexpression of Not3 could reduce tumor formation. Not3 downregulation has a mild but broad effect on gene expression and leads to increased levels of genes involved in DNA replication and ribosome biogenesis. CycB upregulation also contributes to the Not3 tumor phenotype. Similar findings were obtained in human T-ALL cell lines, pointing out the conserved function of Not3. Conclusions Together, our data establish a critical role for Not3 and the entire CCR4-NOT complex as tumor suppressor. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1756-8722 |
| Relation: | http://link.springer.com/article/10.1186/s13045-018-0650-0; https://doaj.org/toc/1756-8722 |
| DOI: | 10.1186/s13045-018-0650-0 |
| Access URL: | https://doaj.org/article/d2b4f3970332452b81f7d13001aa3d14 |
| Accession Number: | edsdoj.2b4f3970332452b81f7d13001aa3d14 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 17568722 |
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| DOI: | 10.1186/s13045-018-0650-0 |
| Published in: | Journal of Hematology & Oncology |
| Language: | English |