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Science 293 (5535): 1651-1653

Copyright © 2001 by the American Association for the Advancement of Science

Regulation of Transcriptional Activation Domain Function by Ubiquitin

Simone E. Salghetti,1 Amy A. Caudy,12 Joshua G. Chenoweth,3 William P. Tansey1*

The ability of transcriptional activation domains (TADs) to signal ubiquitin-mediated proteolysis suggests an involvement of the ubiquitin-proteasome pathway in transcription. To probe this involvement, we asked how ubiquitylation regulates the activity of a transcription factor containing the VP16 TAD. We show that the VP16 TAD signals ubiquitylation through the Met30 ubiquitin-ligase and that Met30 is also required for the VP16 TAD to activate transcription. The requirement for Met30 in transcription is circumvented by fusion of ubiquitin to the VP16 activator, demonstrating that activator ubiquitylation is essential for transcriptional activation. We propose that ubiquitylation regulates TAD function by serving as a dual signal for activation and activator destruction.

1 Cold Spring Harbor Laboratory, 1 Bungtown Road, Post Office Box 100, Cold Spring Harbor, NY 11724, USA.
2 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
3 Graduate Program in Molecular and Cellular Biology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
*   To whom correspondence should be addressed. E-mail: tansey{at}

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Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex.
C. J. Fryer, E. Lamar, I. Turbachova, C. Kintner, and K. A. Jones (2002)
Genes & Dev. 16, 1397-1411
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Emerging Roles of Ubiquitin in Transcription Regulation.
R. C. Conaway, C. S. Brower, and J. W. Conaway (2002)
Science 296, 1254-1258
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Activation of the Murine Type II Transforming Growth Factor-beta Receptor Gene. UP-REGULATION AND FUNCTION OF THE TRANSCRIPTION FACTOR Elf-3/Ert/Esx/Ese-1.
J.-H. Kim, P. J. Wilder, J. Hou, T. Nowling, and A. Rizzino (2002)
J. Biol. Chem. 277, 17520-17530
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TRANSCRIPTION: Proteasome Parts at Gene Promoters.
S. Ottosen, F. J. Herrera, and S. J. Triezenberg (2002)
Science 296, 479-481
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Recruitment of a 19S Proteasome Subcomplex to an Activated Promoter.
F. Gonzalez, A. Delahodde, T. Kodadek, and S. A. Johnston (2002)
Science 296, 548-550
   Abstract »    Full Text »    PDF »
Ubc9 Is a Novel Modulator of the Induction Properties of Glucocorticoid Receptors.
S. Kaul, J. A. Blackford Jr., S. Cho, and S. S. Simons Jr. (2002)
J. Biol. Chem. 277, 12541-12549
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Phosphorylation and O-Linked Glycosylation of Elf-1 Leads to Its Translocation to the Nucleus and Binding to the Promoter of the TCR {zeta}-Chain.
Y.-T. Juang, E. E. Solomou, B. Rellahan, and G. C. Tsokos (2002)
J. Immunol. 168, 2865-2871
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