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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}cshl.org
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- The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms.
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Development
129, 5697-5706
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- New perspectives on the regulation of intermembrane glycerophospholipid traffic.
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J. Lipid Res.
44, 441-449
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- Phosphatidylserine Transport to the Mitochondria Is Regulated by Ubiquitination.
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- Involvement of Proteasome in the Dynamic Assembly of the Androgen Receptor Transcription Complex.
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- Attenuation of Glucocorticoid Signaling through Targeted Degradation of p300 via the 26S Proteasome Pathway.
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Mol. Endocrinol.
16, 2819-2827
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- Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes.
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PNAS
99, 13425-13430
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- EDD, the Human Hyperplastic Discs Protein, Has a Role in Progesterone Receptor Coactivation and Potential Involvement in DNA Damage Response.
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Mol. Cell. Biol.
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- The E2 Ubiquitin Conjugase Rad6 Is Required for the ArgR/Mcm1 Repression of ARG1 Transcription.
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Mol. Cell. Biol.
22, 4011-4019
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- Proteasomal Inhibition Enhances Glucocorticoid Receptor Transactivation and Alters Its Subnuclear Trafficking.
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Mol. Cell. Biol.
22, 4113-4123
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- Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex.
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Genes & Dev.
16, 1397-1411
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- Coordination of ATF6-mediated Transcription and ATF6 Degradation by a Domain That Is Shared with the Viral Transcription Factor, VP16.
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277, 20734-20739
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- Emerging Roles of Ubiquitin in Transcription Regulation.
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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.
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