Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 1 July 2005:
Vol. 309. no. 5731, pp. 142 - 145
DOI: 10.1126/science.1111915
Prev | Table of Contents | Next

Reports

Variable Control of Ets-1 DNA Binding by Multiple Phosphates in an Unstructured Region

Miles A. Pufall,1 Gregory M. Lee,2 Mary L. Nelson,1 Hyun-Seo Kang,2 Algirdas Velyvis,3 Lewis E. Kay,3 Lawrence P. McIntosh,2 Barbara J. Graves1*

Cell signaling that culminates in posttranslational modifications directs protein activity. Here we report how multiple Ca2+-dependent phosphorylation sites within the transcription activator Ets-1 act additively to produce graded DNA binding affinity. Nuclear magnetic resonance spectroscopic analyses show that phosphorylation shifts Ets-1 from a dynamic conformation poised to bind DNA to a well-folded inhibited state. These phosphates lie in an unstructured flexible region that functions as the allosteric effector of autoinhibition. Variable phosphorylation thus serves as a "rheostat" for cell signaling to fine-tune transcription at the level of DNA binding.

1 Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112–5550, USA.
2 Department of Biochemistry and Molecular Biology, Department of Chemistry, and The Michael Smith Laboratory, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
3 Departments of Medical Genetics, Biochemistry, and Chemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.

* To whom correspondence should be addressed. E-mail: Barbara.Graves{at}hci.utah.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus.
M. Zamisch, L. Tian, R. Grenningloh, Y. Xiong, K. F. Wildt, M. Ehlers, I-C. Ho, and R. Bosselut (2009)
J. Exp. Med. 206, 2685-2699
   Abstract »    Full Text »    PDF »
An age-related homeostasis mechanism is essential for spontaneous amelioration of hemophilia B Leyden.
S. Kurachi, J. S. Huo, A. Ameri, K. Zhang, A. C. Yoshizawa, and K. Kurachi (2009)
PNAS 106, 7921-7926
   Abstract »    Full Text »    PDF »
Regulation of C-type Lectin Antimicrobial Activity by a Flexible N-terminal Prosegment.
S. Mukherjee, C. L. Partch, R. E. Lehotzky, C. V. Whitham, H. Chu, C. L. Bevins, K. H. Gardner, and L. V. Hooper (2009)
J. Biol. Chem. 284, 4881-4888
   Abstract »    Full Text »    PDF »
Dynamic equilibrium engagement of a polyvalent ligand with a single-site receptor.
T. Mittag, S. Orlicky, W.-Y. Choy, X. Tang, H. Lin, F. Sicheri, L. E. Kay, M. Tyers, and J. D. Forman-Kay (2008)
PNAS 105, 17772-17777
   Abstract »    Full Text »    PDF »
The RCI server: rapid and accurate calculation of protein flexibility using chemical shifts.
M. V. Berjanskii and D. S. Wishart (2007)
Nucleic Acids Res. 35, W531-W537
   Abstract »    Full Text »    PDF »
Polyelectrostatic interactions of disordered ligands suggest a physical basis for ultrasensitivity.
M. Borg, T. Mittag, T. Pawson, M. Tyers, J. D. Forman-Kay, and H. S. Chan (2007)
PNAS 104, 9650-9655
   Abstract »    Full Text »    PDF »
Bidirectional Activity-Dependent Regulation of Neuronal Ion Channel Phosphorylation.
H. Misonou, M. Menegola, D. P. Mohapatra, L. K. Guy, K.-S. Park, and J. S. Trimmer (2006)
J. Neurosci. 26, 13505-13514
   Abstract »    Full Text »    PDF »
Fli1 and Ets1 Have Distinct Roles in Connective Tissue Growth Factor/CCN2 Gene Regulation and Induction of the Profibrotic Gene Program.
S. S. Nakerakanti, B. Kapanadze, M. Yamasaki, M. Markiewicz, and M. Trojanowska (2006)
J. Biol. Chem. 281, 25259-25269
   Abstract »    Full Text »    PDF »
Graded regulation of the Kv2.1 potassium channel by variable phosphorylation..
K.-S. Park, D. P. Mohapatra, H. Misonou, and J. S. Trimmer (2006)
Science 313, 976-979
   Abstract »    Full Text »    PDF »
The Stimulus-induced Tyrosine Phosphorylation of Munc18c Facilitates Vesicle Exocytosis.
E. Oh and D. C. Thurmond (2006)
J. Biol. Chem. 281, 17624-17634
   Abstract »    Full Text »    PDF »
Phosphorylation by PKA potentiates retinoic acid receptor {alpha} activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7.
E. Gaillard, N. Bruck, Y. Brelivet, G. Bour, S. Lalevee, A. Bauer, O. Poch, D. Moras, and C. Rochette-Egly (2006)
PNAS 103, 9548-9553
   Abstract »    Full Text »    PDF »
Cooperative DNA Binding with AP-1 Proteins Is Required for Transformation by EWS-Ets Fusion Proteins..
S. Kim, C. T. Denny, and R. Wisdom (2006)
Mol. Cell. Biol. 26, 2467-2478
   Abstract »    Full Text »    PDF »
Transcription factor ETS1 is critical for human uterine decidualization.
C. A. Kessler, J. K. Schroeder, A. K. Brar, and S. Handwerger (2006)
Mol. Hum. Reprod. 12, 71-76
   Abstract »    Full Text »    PDF »
Can You Hear Me Now? Regulating Transcriptional Activators by Phosphorylation.
K. H. Gardner and M. Montminy (2005)
Sci. STKE 2005, pe44
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)