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Involvement of the CCR4-NOT Deadenylase Complex in the Control of Cell Growth

  • Masahiro Morita
  • Kentaro Ito
  • Toru Suzuki
  • Tadashi Yamamoto
Conference paper

The Tob/BTG family comprises six proteins, Tob, Tob2, ANA, BTG1, BTG2/PC3/ TIS21, and PC3B, which share a common amino-terminal domain (1). All these proteins, when overexpressed, suppress growth of NIH3T3 cells (2). There is evidence that the Tob/BTG family of proteins is involved in regulation not only of cell growth but also of differentiation and development. For instance, BTG1 is thought to be involved in myogenesis induced by triiodothyronine (3). Analysis of tob-deficient mice revealed that Tob is involved in bone development (4). Although they lack DNA-binding domains, the Tob/BTG proteins are generally viewed as tran-scriptional cofactors. For example, Tob interacts with Smad in BMP2 signaling (4) and in T-cell anergy (5). BTG2 enhances Hoxb9-mediated transcription (6). Both Tob and BTG2 reduce cyclin D1 expression (7,8), possibly by recruiting histone deacetylase to the cyclin D1 promoter (9), contributing to G0/G1 arrest. On the other hand, Tob/Btg family proteins are also implicated in translational regulation by regulating the deadenylase activity or by interacting with the polyA binding proteins (10).

The CCR4-NOT complex is a large (>1 MDa) multi-subunit protein complex and is conserved from yeast to humans (11). The mammalian CCR4-NOT complex consists of 10 Cnot proteins: Cnot1-Cnot4, Ccr4a/Cnot6, Ccr4b/Cnot6L, Caf1/ Cnot7, Pop2/Cnot8, Caf40/Cnot9, and Caf130/Cnot10 (Table 1). Yeast CCR4-NOT has been considered to be a global transcription complex that regulates a variety of genes such as the nonfermentative gene either positively or negatively (11). Accumulating evidence also shows that the mammalian Cnot proteins interact with proteins in the transcription machinery. For example, Cnot1 and Cnot7 are reported to interact with estrogen receptor-α (12,13). Cnot7 is also shown to interact with retinoid X receptor-β (14). Another report showed that Cnot9 is associated with retinoic acid receptor-α (15). Therefore, the mammalian CCR4-NOT complex appears to be involved in various transcription events controlled by the nuclear

Keywords

Prog Nucleic Acid mRNA Deadenylation Deadenylase Activity polyA Binding Protein Estrogen Receptor Alpha Signaling 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2009

Authors and Affiliations

  • Masahiro Morita
    • 1
  • Kentaro Ito
    • 1
  • Toru Suzuki
    • 1
  • Tadashi Yamamoto
    • 1
  1. 1.Division of Oncology, The Institute of Medical ScienceThe University of TokyoMinatok-ku

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