Tristetraprolin Impairs Myc-Induced Lymphoma and Abolishes the Malignant State
| Autor: | Dan A. Dixon, John L. Cleveland, Joanne R. Doherty, Franz X. Schaub, Weimin Li, Meredith A. Steeves, Robert J. Rounbehler, Chunying Yang, Perry J. Blackshear, Mohammad Fallahi, Sandhya Sanduja |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Lymphoma
B-Cell RNA Stability Transgene Tristetraprolin Mice Transgenic Biology medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology law.invention Proto-Oncogene Proteins c-myc Mice law Transcription (biology) Cell Line Tumor Human Umbilical Vein Endothelial Cells medicine Animals Humans ZFP36 Genes Tumor Suppressor RNA Messenger Adaptor Proteins Signal Transducing B-Lymphocytes Biochemistry Genetics and Molecular Biology(all) Signal transducing adaptor protein Molecular biology Mice Inbred C57BL Cell Transformation Neoplastic Cancer research Suppressor Carcinogenesis HeLa Cells |
| Zdroj: | Cell. 150(3):563-574 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2012.06.033 |
| Popis: | SummaryMyc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis. |
| Databáze: | OpenAIRE |
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