The mammalian anti‐proliferative BTG/Tob protein family

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. J. Cell. Physiol. 222:66–72, 2010. © 2009 Wiley‐Liss, Inc.