Abstract:
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Olivero CE,Martínez-Terroba E,Zimmer J,Liao C,Tesfaye E,Hooshdaran N,Schofield JA,Bendor J,Fang D,Simon MD,Zamudio JR,Dimitrova Ndoi
10.1016/j.molcel.2019.12.014subject
Has Abstractpub_date
2020-02-20 00:00:00pages
761-774.e8issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(19)30927-Xjournal_volume
77pub_type
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