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Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex

Takashi Miyasaka1, Masahiro Morita, Kentaro Ito

  • 1Division of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo 108-8639, Japan.

Cancer Science
|April 2, 2008
PubMed

Insights

Tob protein suppresses cell growth by interacting with the CCR4-NOT complex, a key regulator of gene expression. This interaction affects mRNA stability, revealing new mechanisms for Tob

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gene Regulation

Background:

  • Tob protein overexpression inhibits NIH3T3 cell growth, potentially via regulating growth-related genes.
  • The precise molecular mechanisms of Tob-mediated gene regulation remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanisms of Tob protein's function in gene expression regulation.
  • To identify proteins that interact with Tob using a proteomics approach.

Main Methods:

  • Establishment of stable Tob-expressing cell lines.
  • Proteomics analysis to identify Tob-interacting proteins.
  • In vitro assays to assess the effect of Tob on the CCR4-NOT complex's deadenylase activity.

Main Results:

  • Tob protein was found to associate with the CCR4-NOT complex.
  • The carboxyl-terminal region of Tob specifically interacted with Cnot1, a core component of the CCR4-NOT complex.
  • Tob suppressed the deadenylase activity of the CCR4-NOT complex in vitro.

Conclusions:

  • Tob protein regulates gene expression post-transcriptionally by influencing mRNA stability through interaction with the CCR4-NOT complex.
  • This post-transcriptional regulation contributes to Tob's previously observed antiproliferative effects, complementing its known transcriptional roles.

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