The BTG/Tob protein family, which consists of six members, including TOB1, TOB2, BTG1, BTG2/PC3/TIS21, BTG3/ANA and BTG4/PC3B, are negative regulators of the cell cycle that help to prevent uncontrolled cell proliferation (3).
TOB1 expression suppresses the transcription of positive cell cycle regulators, including IL2, IL4, IFNg, cyclin E and cyclin A, inhibiting cell proliferation (4). BTG/TOB proteins also inhibit cell proliferation by potentially enhancing deadenylation. TOB2 promotes deadenylation by recruiting Caf1 deadenylase to the mRNA poly(A) tail. This recruitment occurs through the interaction of TOB2 with Caf1 and poly(A)-binding protein (PABP).
BTG1 is another antiproliferative mediator whose expression peaks in the G0/G1 phases of the cell cycle and drops as cells move through G1. BTG2 negatively regulates the cell cycle checkpoint from the G1 to S phase by suppressing cyclin D1 promoter activity. BTG3 binds to transcription factor E2F1 to regulate cell proliferation and the G2 checkpoint (5). BTG4 induces G1 and G2 arrest in the cell cycle by targeting the CD1/CDK4 pathway, the cyclin E pathway or transcription factors PRMT1 and CAF-1 (6).