The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability
Open accessAbstract
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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Citations
Cites
Regulation of translation initiation by FRAP/mTOR
Gingras, A.-C., Raught, B., & Sonenberg, N. (2001) · Genes & Development · doi:10.1101/gad.887201 · Cited by 1,545
Life on a planet of its own: Regulation of RNA polymerase I transcription in the nucleolus
Grummt, I. (2003) · Genes & Development · doi:10.1101/gad.1098503r · Cited by 540
Self-citationp53 represses ribosomal gene transcription
Budde, A., & Grummt, I. (1999) · Oncogene · doi:10.1038/sj.onc.1202402 · Cited by 157
Self-citationAlbers, M. W., Williams, R. T., Brown, E. J., Tanaka, A., Hall, F. L., & Schreiber, S. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41602-x · Cited by 145
Cited by
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
mTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737
Metadata
- Authors
- Mayer, C., Zhao, J., Yuan, X., & Grummt, I.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-02-15
- Volume
- 18
- Issue
- 4
- Pages
- 423-434
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2130623329
- Cited by
- 505
- References
- 4
- Type
- posted content
- Language
- en
- Open access
- diamond
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