mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability

Genes and Development - Tập 18 Số 4 - Trang 423-434 - 2004
Christine Mayer1, Jian Zhao2, Xuejun Yuan2, Ingrid Grummt3
1Division of Molecular Biology of the Cell II, German Cancer Research Center, D-69120 Heidelberg, Germany
2German Cancer Research Center (dkfz
3Cell Biology and Tumor Biology

Tóm tắt

In cycling cells, transcription of ribosomal RNA genes by RNA polymerase I (Pol I) is tightly coordinated with cell growth. Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability. Inhibition of mTOR signaling by rapamycin inactivates TIF-IA and impairs transcription-initiation complex formation. Moreover, rapamycin treatment leads to translocation of TIF-IA into the cytoplasm. Rapamycin-mediated inactivation of TIF-IA is caused by hypophosphorylation of Ser 44 (S44) and hyperphosphorylation of Ser 199 (S199). Phosphorylation at these sites affects TIF-IA activity in opposite ways, for example, phosphorylation of S44 activates and S199 inactivates TIF-IA. The results identify a new target for mTOR-signaling pathways and elucidate the molecular mechanism underlying mTOR-dependent regulation of rRNA synthesis.

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Genes and Development

Tập 18 Số 4

423-434

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