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

K. Tago, Megumi Tago, H. Itoh, Y. Furukawa, J. Kikuchi, T. Kato, K. Suzuki, K. Yanagisawa

Research output: Contribution to journalArticle

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Abstract

Tumor suppressor protein p19(ARF) (Arf; p14(ARF) 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.

Original languageEnglish
Pages (from-to)314-322
Number of pages9
JournalOncogene
Volume34
Issue number3
DOIs
Publication statusPublished - 2015 Jan 15

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Neoplasms
Proteins
DEAD-box RNA Helicases
Tumor Suppressor Protein p14ARF
Tumor Suppressor Proteins
myc Genes
Proto-Oncogenes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Tago, K., Tago, M., Itoh, H., Furukawa, Y., Kikuchi, J., Kato, T., ... Yanagisawa, K. (2015). Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5. Oncogene, 34(3), 314-322. https://doi.org/10.1038/onc.2013.561

Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5. / Tago, K.; Tago, Megumi; Itoh, H.; Furukawa, Y.; Kikuchi, J.; Kato, T.; Suzuki, K.; Yanagisawa, K.

In: Oncogene, Vol. 34, No. 3, 15.01.2015, p. 314-322.

Research output: Contribution to journalArticle

Tago, K, Tago, M, Itoh, H, Furukawa, Y, Kikuchi, J, Kato, T, Suzuki, K & Yanagisawa, K 2015, 'Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5', Oncogene, vol. 34, no. 3, pp. 314-322. https://doi.org/10.1038/onc.2013.561
Tago, K. ; Tago, Megumi ; Itoh, H. ; Furukawa, Y. ; Kikuchi, J. ; Kato, T. ; Suzuki, K. ; Yanagisawa, K. / Arf tumor suppressor disrupts the oncogenic positive feedback loop including c-Myc and DDX5. In: Oncogene. 2015 ; Vol. 34, No. 3. pp. 314-322.
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