BTG family proteins and cell cycle regulation
BTG2 is found to be one of the immediate early genes up-regulated by neural growth factor (NGF) and epidermal growth factor (EGF). Its transcriptional level is also up-regulated by p53, gamma radiation, adriamycin and UV treatment of cells. BTG seems to be important for the cell cycle progression as BTG2 is preferentially expressed in quiescent cells. Over-expression of BTG2 decreases the growth of NIH3T3 cells and induces neuronal differentiation and prevention apoptosis of PC12 cells. Molecularly, BTG2 expression induces hypophosphorylation of RB and G1 arrest which could be rescued by overexpression of cyclin D1. BTG1 and BTG2 interact with PRMT1 (predominant cellular arginine N-methyltransferase) and increase PRMT1 methyltransferase activity. Box C domain in BTG1 and 2 are responsible for the interaction. Box C domain alone acts as a dominant negative which blocks PRMT1 activity. PRMT1 activity is essential for NGF induced PC12 differentiation, and blocking PRMT1 by Box C domain of BTG1 or 2 induces apoptosis. In addition, BTG2 and HoxB9 interaction enhances the transcription of Hoxb9. Lastly, association of BTG2 and BTG1 with Caf1 is also reported to modulates transcriptional activity of CAF1.
Contributor: Yen-Liang Chen, PhD
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