Martin Dietmar E, Soulard Alexandre, Hall Michael N
Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Cell. 2004 Dec 29;119(7):969-79. doi: 10.1016/j.cell.2004.11.047.
The regulation of ribosome biogenesis in response to environmental conditions is a key aspect of cell growth control. Ribosomal protein (RP) genes are regulated by the nutrient-sensitive, conserved target of rapamycin (TOR) signaling pathway. TOR controls the subcellular localization of protein kinase A (PKA) and the PKA-regulated kinase YAK1. However, the target transcription factor(s) of the TOR-PKA pathway are unknown. We show that regulation of RP gene transcription via TOR and PKA in yeast involves the Forkhead-like transcription factor FHL1 and the two cofactors IFH1 (a coactivator) and CRF1 (a corepressor). TOR, via PKA, negatively regulates YAK1 and maintains CRF1 in the cytoplasm. Upon TOR inactivation, activated YAK1 phosphorylates and activates CRF1. Phosphorylated CRF1 accumulates in the nucleus and competes with IFH1 for binding to FHL1 at RP gene promoters, and thereby inhibits transcription of RP genes. Thus, we describe a signaling mechanism linking an environmental sensor to ribosome biogenesis.
核糖体生物合成对环境条件的响应调控是细胞生长控制的一个关键方面。核糖体蛋白（RP）基因受营养敏感的、保守的雷帕霉素靶蛋白（TOR）信号通路调控。TOR控制蛋白激酶A（PKA）和PKA调控的激酶YAK1的亚细胞定位。然而，TOR-PKA通路的靶转录因子尚不清楚。我们发现，酵母中通过TOR和PKA对RP基因转录的调控涉及叉头样转录因子FHL1以及两个辅因子IFH1（一种共激活因子）和CRF1（一种共抑制因子）。TOR通过PKA负调控YAK1并使CRF1维持在细胞质中。TOR失活后，激活的YAK1使CRF1磷酸化并激活。磷酸化的CRF1在细胞核中积累，并与IFH1竞争在RP基因启动子处与FHL1结合，从而抑制RP基因的转录。因此，我们描述了一种将环境传感器与核糖体生物合成联系起来的数据机制。
