p53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis
| Autor: | Clara Liao, Nima Hooshdaran, Jeremy A. Schofield, Nadya Dimitrova, Jesse R. Zamudio, Christiane E. Olivero, Matthew D. Simon, Jordan Bendor, Elena Martínez-Terroba, Ephrath Tesfaye, Dorthy Fang, Joshua T. Zimmer |
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| Rok vydání: | 2019 |
| Předmět: |
Gene isoform
Lung Neoplasms Carcinogenesis Biology medicine.disease_cause Proto-Oncogene Mas Article Cell Line Proto-Oncogene Proteins c-myc 03 medical and health sciences Mice 0302 clinical medicine Transcription (biology) Stress Physiological medicine Animals Humans Promoter Regions Genetic Molecular Biology Gene Cells Cultured 030304 developmental biology Cell Proliferation 0303 health sciences RNA Cell Biology Chromatin PVT1 Cell biology Mice Inbred C57BL Enhancer Elements Genetic Gene Expression Regulation Tumor progression RNA Long Noncoding Tumor Suppressor Protein p53 030217 neurology & neurosurgery |
| Zdroj: | Mol Cell |
| ISSN: | 1097-4164 |
| Popis: | Summary The tumor suppressor p53 transcriptionally activates target genes to suppress cellular proliferation during stress. p53 has also been implicated in the repression of the proto-oncogene Myc, but the mechanism has remained unclear. Here, we identify Pvt1b, a p53-dependent isoform of the long noncoding RNA (lncRNA) Pvt1, expressed 50 kb downstream of Myc, which becomes induced by DNA damage or oncogenic signaling and accumulates near its site of transcription. We show that production of the Pvt1b RNA is necessary and sufficient to suppress Myc transcription in cis without altering the chromatin organization of the locus. Inhibition of Pvt1b increases Myc levels and transcriptional activity and promotes cellular proliferation. Furthermore, Pvt1b loss accelerates tumor growth, but not tumor progression, in an autochthonous mouse model of lung cancer. These findings demonstrate that Pvt1b acts at the intersection of the p53 and Myc transcriptional networks to reinforce the anti-proliferative activities of p53. |
| Databáze: | OpenAIRE |
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