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Structural Basis for DNA Recognition by FoxO1 and Its Regulation by Posttranslational Modification
Open accessAbstract
SUMMARY FoxO transcription factors regulate the transcription of genes that control metabolism, cellular proliferation, stress tolerance and possibly lifespan. A number of post-translational modifications within the forkhead DNA binding domain regulate FoxO mediated transcription. We report the crystal structures of FoxO1 bound to three different DNA elements and measure the change in FoxO1-DNA affinity with acetylation and phosphorylation. The structures reveal additional contacts and increased DNA distortion for the highest affinity DNA site. The flexible wing 2 region of the forkhead domain was not observed in the structures but is necessary for DNA-binding, and we show that p300 acetylation in wing 2 reduces DNA affinity. We also show that MST1 phosphorylation of FoxO1 prevents high affinity DNA binding. The observation that FoxO-DNA affinity varies between response elements and with post-translational modifications suggests that modulation of FoxO-DNA affinity is an important component of FoxO regulation in health and misregulation in disease.
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Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562
IκB Kinase Promotes Tumorigenesis through Inhibition of Forkhead FOXO3a
Hu, M. C.-T., Lee, D.-F., Xia, W., Golfman, L. S., Ou-Yang, F., Yang, J.-Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00302-2 · Cited by 868
Cited by
Redox regulation of FoxO transcription factors
Klotz, L.-O., Sánchez-Ramos, C., Prieto-Arroyo, I., Urbánek, P., Steinbrenner, H., & Monsalve, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.06.019 · Cited by 747
FoxO transcription factors; Regulation by AKT and 14-3-3 proteins
Tzivion, G., Dobson, M., & Ramakrishnan, G. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.06.002 · Cited by 728
Mihaylova, M. M., Vasquez, D. S., Ravnskjaer, K., Denechaud, P.-D., Yu, R. T., Alvarez, J. G., Downes, M., Evans, R. M., Montminy, M., & Shaw, R. J. (2011) · Cell · doi:10.1016/j.cell.2011.03.043 · Cited by 533
Insulin/insulin-like growth factor signaling in C. elegans
Murphy, C. T. (2013) · WormBook · doi:10.1895/wormbook.1.164.1 · Cited by 532
FOXO Transcription Factors: Their Clinical Significance and Regulation
Wang, Y., Zhou, Y., & Graves, D. T. (2014) · BioMed Research International · doi:10.1155/2014/925350 · Cited by 419
Metadata
- Authors
- Brent, M. M., Anand, R., & Marmorstein, R.
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 16
- Issue
- 9
- Pages
- 1407-1416
- ISSN
- 0969-2126 (ISSN-L)
- OpenAlex
- W1998674552
- Cited by
- 196
- References
- 3
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- bronze
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