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Cell Cycle Control by BTG Proteins

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BTG2 (BTG Family Member-2) is endowed with antiproliferative activity. The expression of BTG2 in cycling cells induces accumulation of hypophosphorylated, growth-inhibitory forms of Rb (Retinoblastoma) and led to G1 arrest through impairment of DNA synthesis. Overexpression of CcnD1 (Cyclin-D1) counteracts G1 arrest. Rb is a nuclear phosphoprotein whose phosphorylation state oscillates regularly during the cell cycle. Its under-phosphorylated forms predominate in G0 and G1, while highly phosphorylated forms exist in S, G2 and M phases (Ref.1). The primary biological function of under-phosphorylated Rb is to inhibit progression toward S phase by controlling a checkpoint in late G1. In fact, under-phosphorylated Rb associates with members of the E2F family of transcription factors, impairing their activity and leading to a cell cycle [...]


1.Arrest of G (1)-S progression by the p53-inducible gene PC3 is Rb dependent and relies on the inhibition of cyclin D1 transcription.
Guardavaccaro D, Corrente G, Covone F, Micheli L, D'Agnano I, Starace G, Caruso M, Tirone F.
Mol. Cell Biol. 2000 Mar; 20(5):1797-815.
2.Induction of growth inhibition of 293 cells by downregulation of the cyclin E and cyclin-dependent kinase 4 proteins due to overexpression of TIS21.
Lim IK, Lee MS, Ryu MS, Park TJ, Fujiki H, Eguchi H, Paik WK.
Mol. Carcinog. 1998 Sep; 23(1):25-35.
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