Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5

K. Tago, M. Funakoshi-Tago, H. Itoh, Y. Furukawa, J. Kikuchi, T. Kato, K. Suzuki, K. Yanagisawa

研究成果: Article査読

15 被引用数 (Scopus)

抄録

Tumor suppressor protein p19ARF (Arf; p14ARF in humans) functions in both p53-dependent and -independent modes to counteract hyper-proliferative signals caused by proto-oncogene activation, but its p53-independent activities remain poorly understood. Using the tandem affinity purification-tag technique, we purified Arf-containing protein complexes and identified p68 DEAD-box protein (DDX5) as a novel interacting protein of Arf. In this study, we found that DDX5 interacts with c-Myc, and harbors essential roles for c-Myc-mediated transcription and its transforming activity. Furthermore, when c-Myc was forcibly expressed, the expression level of DDX5 protein was drastically increased through the acceleration of protein synthesis of DDX5, suggesting the presence of an oncogenic positive feedback loop including c-Myc and DDX5. Strikingly, Arf blocked the physical interaction between DDX5 and c-Myc, and drove away DDX5 from the promoter of c-Myc target genes. These observations most likely indicate the mechanism by which Arf causes p53-independent tumor-suppressive activity.

本文言語English
ページ(範囲)310-318
ページ数9
ジャーナルOncogene
34
3
DOI
出版ステータスPublished - 2015 1 15

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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