RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis.
RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis.
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DOI：
10.1158/0008-5472.can-11-1472
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发表时间：
2011-11-01
期刊：
影响因子：
11.2
通讯作者：
Weber JD
中科院分区：
文献类型：
--
作者：
Saporita AJ;Chang HC;Winkeler CL;Apicelli AJ;Kladney RD;Wang J;Townsend RR;Michel LS;Weber JD
The p19ARF tumor suppressor limits ribosome biogenesis and responds to hyperproliferative signals to activate the p53 checkpoint response. While its activation of p53 has been well characterized, ARF’s role 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, since 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.
