RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis

Anthony J. Saporita, Hsiang Chun Chang, Crystal L. Winkeler, Anthony J. Apicelli, Raleigh D. Kladney, Jianbo Wang, R. Reid Townsend, Loren S. Michel, Jason D. Weber

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The p19ARF tumor suppressor limits ribosome biogenesis and responds to hyperproliferative signals to activate the p53 checkpoint response. Although its activation of p53 has been well characterized, the role of ARF in restraining nucleolar ribosome production is poorly understood. Here we report the use of a mass spectroscopic analysis to identify protein changes within the nucleoli of Arf-deficient mouse cells. Through this approach, we discovered that ARF limited the nucleolar localization of the RNA helicase DDX5, which promotes the synthesis and maturation of rRNA, ultimately increasing ribosome output and proliferation. ARF inhibited the interaction between DDX5 and nucleophosmin (NPM), preventing association of DDX5 with the rDNA promoter and nuclear pre-ribosomes. In addition, Arf-deficient cells transformed by oncogenic RasV12 were addicted to DDX5, because reduction of DDX5 was sufficient to impair RasV12-driven colony formation in soft agar and tumor growth in mice. Taken together, our findings indicate that DDX5 is a key p53-independent target of the ARF tumor suppressor and is a novel non-oncogene participant in ribosome biogenesis.

Original languageEnglish
Pages (from-to)6708-6717
Number of pages10
JournalCancer research
Volume71
Issue number21
DOIs
StatePublished - Nov 1 2011

Fingerprint

Dive into the research topics of 'RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis'. Together they form a unique fingerprint.

Cite this