RNA polymerase III transcription is repressed in response to the tumour suppressor ARF

Jennifer P Morton1, Theodoros Kantidakis, Robert J White

  • 1Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, UK.

Nucleic Acids Research
|April 19, 2007
PubMed

Insights

The tumor suppressor ARF inhibits tRNA synthesis, a process dependent on the p53 protein. This reveals a new p53-dependent mechanism by which ARF controls cell growth and proliferation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • The tumor suppressor protein ARF defends against hyperproliferation caused by oncogene activation.
  • ARF is often silenced or deleted in human cancers.
  • ARF activation can halt cell growth and cycle progression or induce apoptosis, often by stabilizing p53 via MDM2 inhibition.

Purpose of the Study:

  • To investigate the role of ARF in regulating tRNA synthesis.
  • To determine if ARF's inhibition of tRNA synthesis is p53-dependent.

Main Methods:

  • Investigated the effect of ARF on tRNA synthesis.
  • Examined ARF's impact on tRNA gene transcription in the presence and absence of p53.

Main Results:

  • ARF was found to inhibit the synthesis of tRNA.
  • Unlike its p53-independent suppression of rRNA synthesis, ARF's inhibition of tRNA gene transcription requires the presence of p53.

Conclusions:

  • ARF regulates tRNA synthesis through a p53-dependent pathway.
  • This adds tRNA synthesis inhibition to the list of cellular changes induced by ARF.

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