The mammalian anti-proliferative BTG/Tob protein family.
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.
Winkler
G Sebastiaan
GS
School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, United Kingdom. sebastiaan.winkler@nottingham.ac.uk
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D049109:Cell Proliferation; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins