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The mammalian anti-proliferative BTG/Tob protein family
1School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, United Kingdom. sebastiaan.winkler@nottingham.ac.uk
Abstract:
The mammalian BTG/Tob family comprises six proteins (BTG1, BTG2/PC3/Tis21, BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2), which regulate cell cycle progression in a variety of cell types. They are characterised by the conserved N-terminal domain spanning 104-106 amino acids. Recent biochemical and structural data indicate that the conserved BTG domain is a protein-protein interaction module, which is capable of binding to DNA-binding transcription factors as well as the paralogues CNOT7 (human Caf1/Caf1a) and CNOT8 (human Pop2/Calif/Caf1b), two deadenylase subunits of the Ccr4-Not complex. Consistent with this finding, several members of the BTG/Tob family are shown to be implicated in transcription in the nucleus and cytoplasmic mRNA deadenylation and turnover. The C-terminal regions are less conserved and appear to mediate protein-protein interactions that are unique to each family member. The human and mouse BTG/Tob proteins will be the focus of this review and structural aspects of BTG/Tob interactions with components of the Ccr4-Not complex, and the role of the BTG/Tob proteins in the regulation of gene expression, tumourigenesis and cancer will be discussed.
Insights
The BTG/Tob protein family regulates cell cycle and gene expression. These proteins interact with transcription factors and Ccr4-Not complex components, impacting mRNA turnover and potentially cancer development.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The mammalian BTG/Tob protein family consists of six members involved in cell cycle regulation across various cell types.
- These proteins share a conserved N-terminal BTG domain (104-106 amino acids) crucial for protein-protein interactions.
Purpose of the Study:
- To review the human and mouse BTG/Tob proteins.
- To discuss structural aspects of BTG/Tob interactions with Ccr4-Not complex components.
- To elucidate the role of BTG/Tob proteins in gene expression regulation, tumorigenesis, and cancer.
Main Methods:
- Biochemical and structural data analysis.
- Review of existing literature on BTG/Tob protein functions.
- Focus on interactions with DNA-binding transcription factors and Ccr4-Not complex subunits (CNOT7, CNOT8).
Main Results:
- The conserved BTG domain acts as a protein-protein interaction module.
- BTG/Tob proteins bind to transcription factors and Ccr4-Not deadenylase subunits.
- Members are involved in nuclear transcription and cytoplasmic mRNA deadenylation/turnover.
- Less conserved C-terminal regions mediate unique interactions.
Conclusions:
- BTG/Tob proteins are key regulators of gene expression through interactions with transcription and mRNA decay machinery.
- Dysregulation of BTG/Tob proteins may contribute to tumorigenesis and cancer progression.
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