P53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Jan 25

PMID 31973890

Citations 88

Authors

Christiane E Olivero

Elena Martinez-Terroba

Joshua Zimmer

Clara Liao

Ephrath Tesfaye

Nima Hooshdaran

Jeremy A Schofield

Jordan Bendor

Dorthy Fang

Matthew D Simon

Jesse R Zamudio

Nadya Dimitrova

Affiliations

Soon will be listed here.

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.

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