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mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability
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Zeitschriftentitel: | Genes & Development |
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Personen und Körperschaften: | , , , |
In: | Genes & Development, 18, 2004, 4, S. 423-434 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Cold Spring Harbor Laboratory
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Schlagwörter: |
Zusammenfassung: | <jats:p>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.</jats:p> |
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Umfang: | 423-434 |
ISSN: |
0890-9369
1549-5477 |
DOI: | 10.1101/gad.285504 |