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ERK-Dependent Phosphorylation of the Transcription Initiation Factor TIF-IA Is Required for RNA Polymerase I Transcription and Cell Growth
Open accessAbstract
Phosphorylation of transcription factors by mitogen-activated protein kinase (MAPK) cascades links cell signaling with the control of gene expression. Here we show that growth factors induce rRNA synthesis by activating MAPK-dependent signaling cascades that target the RNA polymerase I-specific transcription initiation factor TIF-IA. Activation of TIF-IA and ribosomal gene transcription is sensitive to PD98059, indicating that TIF-IA is targeted by MAPK in vivo. Phosphopeptide mapping and mutational analysis reveals two serine residues (S633 and S649) that are phosphorylated by ERK and RSK kinases. Replacement of S649 by alanine inactivates TIF-IA, inhibits pre-rRNA synthesis, and retards cell growth. The results provide a link between growth factor signaling, ribosome production, and cell growth, and may have a major impact on the mechanism of cell transformation.
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Cites
p53 represses ribosomal gene transcription
Budde, A., & Grummt, I. (1999) · Oncogene · doi:10.1038/sj.onc.1202402 · Cited by 157
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Cited by
Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases
Cargnello, M., & Roux, P. P. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00031-10 · Cited by 3,274
ERK signalling: A master regulator of cell behaviour, life and fate
Lavoie, H., Gagnon, J., & Therrien, M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0255-7 · Cited by 1,185
Kunath, T., Saba-El-Leil, M. K., Almousailleakh, M., Wray, J., Meloche, S., & Smith, A. (2007) · Development · doi:10.1242/dev.02880 · Cited by 801
The RSK family of kinases: emerging roles in cellular signalling
Anjum, R., & Blenis, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2509 · Cited by 777
Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription
Ford, E., Voit, R., Liszt, G., Magin, C., Grummt, I., & Guarente, L. (2006) · Genes & Development · doi:10.1101/gad.1399706 · Cited by 629
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Metadata
- Authors
- Zhao, J., Yuan, X., Frödin, M., & Grummt, I.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 11
- Issue
- 2
- Pages
- 405-413
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1991691204
- Cited by
- 258
- References
- 1
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zhao, J., Yuan, X., Frödin, M., & Grummt, I. (2003). ERK-Dependent Phosphorylation of the Transcription Initiation Factor TIF-IA Is Required for RNA Polymerase I Transcription and Cell Growth. Molecular Cell. https://doi.org/10.1016/s1097-2765(03)00036-4
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