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A putative stimulatory role for activator turnover in gene expression

Lipford, J. Russell and Smith, Geoffrey T. and Chi, Yong and Deshaies, Raymond J. (2005) A putative stimulatory role for activator turnover in gene expression. Nature, 438 (7064). pp. 113-116. ISSN 0028-0836.

[img] MS Word (Supplementary Table 1 and 2, Supplementary Figure Legends, Supplementary Methods, and Supplementary Discussion. This file also contains details of NIH support) - Supplemental Material
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[img] PDF (Supplementary Figure 1 Proteasome inhibition represses the transcription of many Gcn4 targets and of INO1, a target of the transcriptional activators, Ino2 and Ino4) - Published Version
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[img] PDF (Supplementary Figure 2 Gal4-TAP functions similarly to wild-type Gal4. pdr5delta, GAL4-TAP strains were treated as in Fig. 1b) - Supplemental Material
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[img] PDF (Supplementary Figure 3 Proteasome inhibition does not affect the dynamic association of Gal80 with a Gal4 target) - Supplemental Material
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[img] PDF (Supplementary Figure 4 Gcn4 is required for the association of RNA polymerase II (polII) with HIS4) - Supplemental Material
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The ubiquitin–proteasome system (UPS) promotes the destruction of target proteins by attaching to them a ubiquitin chain that is recognized by the 26S proteasome. The UPS influences most cellular processes, and its targets include transcriptional activators that are primary determinants of gene expression. Emerging evidence indicates that non-proteolytic functions of the UPS might stimulate transcriptional activity. Here we show that the proteolysis of some transcriptional activators by the UPS can stimulate their function. We focused on the role of UPS-dependent proteolysis in the function of inducible transcriptional activators in yeast, and found that inhibition of the proteasome reduced transcription of the targets of the activators Gcn4, Gal4 and Ino2/4. In addition, mutations in SCF^(Cdc4), the ubiquitin ligase for Gcn4 (ref. 5), or mutations in ubiquitin that prevent degradation, also impaired the transcription of Gcn4 targets. These transcriptional defects were manifested despite the enhanced abundance of Gcn4 on cognate promoters. Proteasome inhibition also decreased the association of RNA polymerase II with Gcn4, Gal4 and Ino2/4 targets, as did mutations in SCFCdc4 for Gcn4 targets. Expression of a stable phospho-site mutant of Gcn4 (ref. 7) or disruption of the kinases that target Gcn4 for turnover alleviated the sensitivity of Gcn4 activity to defects in the UPS.

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Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2005 Nature Publishing Group. Received 2 June 2005; Accepted 3 August 2005. We thank D. Finley, D. H. Wolf, R. Young, A. Hinnebusch, J. Shaw, B. Westermann, J. Nunnari and G. Braus for gifts of strains and reagents; B. Tansey for communicating results before publication; and J. Shaw, B. Westermann, J. Nunnari, S. Sadis, A. Ansari and the members of the Deshaies laboratory for comments and criticism. This work was supported in part by an NIH Research Project Grant to R.J.D. R.J.D. is an Investigator of the Howard Hughes Medical Institute. J.R.L. was supported by an NIH National Research Service Award and a Caltech-Amgen Postdoctoral Fellowship.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Caltech-Amgen Postdoctoral FellowshipUNSPECIFIED
Issue or Number:7064
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56069
Deposited By: Tony Diaz
Deposited On:25 Mar 2015 19:22
Last Modified:03 Oct 2019 08:11

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