Proteasomal degradation of Sfp1 contributes to the repression of ribosome biogenesis during starvation and is mediated by the proteasome activator Blm10

Lopez, Antonio Diaz; Tar, Krisztina; Krügel, Undine; Dange, Thomas; Ros, Ignacio Guerrero; Schmidt, Marion

doi:10.1091/mbc.e10-04-0352

Cited by 43 publications

(60 citation statements)

References 72 publications

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“…Alternatively, suppression of ubi4⌬ by mutations affecting proteasome activity could result from changes in Ub-RP expression without altering ubiquitin degradation. Consistent with this hypothesis, proteasomal degradation of the Sfp1 transcription factor is required for repression of RP (and presumably Ub-RP) gene expression during nutrient limitation (41).…”

Section: Discussionmentioning

confidence: 64%

Activation of the Yeast UBI4 Polyubiquitin Gene by Zap1 Transcription Factor via an Intragenic Promoter Is Critical for Zinc-deficient Growth

MacDiarmid

Taggart

Jeong

et al. 2016

Journal of Biological Chemistry

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Stability of many proteins requires zinc. Zinc deficiency disrupts their folding, and the ubiquitin-proteasome system may help manage this stress. In Saccharomyces cerevisiae, UBI4 encodes five tandem ubiquitin monomers and is essential for growth in zinc-deficient conditions. Although UBI4 is only one of four ubiquitin-encoding genes in the genome, a dramatic decrease in ubiquitin was observed in zinc-deficient ubi4⌬ cells. The three other ubiquitin genes were strongly repressed under these conditions, contributing to the decline in ubiquitin. In a screen for ubi4⌬ suppressors, a hypomorphic allele of the RPT2 proteasome regulatory subunit gene (rpt2 E301K ) suppressed the ubi4⌬ growth defect. The rpt2 E301K mutation also increased ubiquitin accumulation in zinc-deficient cells, and by using a ubiquitin-independent proteasome substrate we found that proteasome activity was reduced. These results suggested that increased ubiquitin supply in suppressed ubi4⌬ cells was a consequence of more efficient ubiquitin release and recycling during proteasome degradation. Degradation of a ubiquitin-dependent substrate was restored by the rpt2 E301K mutation, indicating that ubiquitination is rate-limiting in this process. The UBI4 gene was induced ϳ5-fold in low zinc and is regulated by the zinc-responsive Zap1 transcription factor. Surprisingly, Zap1 controls UBI4 by inducing transcription from an intragenic promoter, and the resulting truncated mRNA encodes only two of the five ubiquitin repeats. Expression of a short transcript alone complemented the ubi4⌬ mutation, indicating that it is efficiently translated. Loss of Zap1-dependent UBI4 expression caused a growth defect in zinc-deficient conditions. Thus, the intragenic UBI4 promoter is critical to preventing ubiquitin deficiency in zinc-deficient cells.Zinc is an essential element with diverse roles in biology. Unlike transition metals, such as iron and copper, zinc ions (Zn 2ϩ ) are not redox-active under physiological conditions and do not play a direct role in redox reactions. Zn 2ϩ strongly interacts with ligands, such as cysteine, histidine, and acidic amino acids in proteins (1). When bound by three or fewer ligands, Zn 2ϩ can act as a Lewis acid to facilitate catalysis by diverse classes of enzymes, including oxidoreductases, transferases, and hydrolases (2). In contrast, binding of Zn 2ϩ by four ligands produces a relatively inert, structurally rigid tetrahedral complex, which provides stability to many classes of protein domains (1-3). Because of its catalytic and structural roles, Zn 2ϩ has been estimated to be required for the folding and function of ϳ10% of proteins encoded by eukaryotic genomes and ϳ5% of proteins in prokaryotes (4, 5). One abundant example is the enzyme alcohol dehydrogenase, which contains two Zn 2ϩ atoms per subunit, one serving in catalysis and the other playing a structural role (1, 6, 7). Consistent with the importance of zinc to Adh 2 folding, mutants of Adh lacking structural zinc site ligands are unstable and quickly degraded in ...

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Section: Discussionmentioning

confidence: 64%

Activation of the Yeast UBI4 Polyubiquitin Gene by Zap1 Transcription Factor via an Intragenic Promoter Is Critical for Zinc-deficient Growth

MacDiarmid

Taggart

Jeong

et al. 2016

Journal of Biological Chemistry

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“…An aperture in Blm10, though small, could provide access to the CP channel for an unfolded protein. Perhaps in this way, Blm10 promotes degradation of Sfp1, a transcriptional activator of ribosomal protein genes Lopez et al 2011). Blm10 also participates in assembly of the CP (Fehlker et al 2003;Marques et al 2007).…”

Section: Regulatory Particlementioning

confidence: 99%

The Ubiquitin–Proteasome System of Saccharomyces cerevisiae

et al. 2012

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Protein modifications provide cells with exquisite temporal and spatial control of protein function. Ubiquitin is among the most important modifiers, serving both to target hundreds of proteins for rapid degradation by the proteasome, and as a dynamic signaling agent that regulates the function of covalently bound proteins. The diverse effects of ubiquitylation reflect the assembly of structurally distinct ubiquitin chains on target proteins. The resulting ubiquitin code is interpreted by an extensive family of ubiquitin receptors. Here we review the components of this regulatory network and its effects throughout the cell.

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“…These data suggest that the function of Blm10 during the final steps of proteasome maturation can be compensated by the RP and that activator binding to the CP in general is required for the final activation of the CP (23). After completion of proteasome biogenesis, Blm10 remains stably bound to the CP and affects the turnover of proteasome substrates (24).…”

mentioning

confidence: 90%

Blm10 Protein Promotes Proteasomal Substrate Turnover by an Active Gating Mechanism

Dange

Smith

Noy

et al. 2011

Journal of Biological Chemistry

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107

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Background: Association of the proteasome core with activators regulates proteasome activity. Results: Blm10 association increases proteasome activity toward peptides and the unstructured proteasome substrate tau-441. This process is mediated by the C terminus of Blm10. Conclusion: C-terminal docking-mediated proteasome activation by Blm10 facilitates the turnover of peptide and protein substrates. Significance: Blm10 contributes to the regulation of proteasome activity.

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Proteasomal degradation of Sfp1 contributes to the repression of ribosome biogenesis during starvation and is mediated by the proteasome activator Blm10

Cited by 43 publications

References 72 publications

Activation of the Yeast UBI4 Polyubiquitin Gene by Zap1 Transcription Factor via an Intragenic Promoter Is Critical for Zinc-deficient Growth

Activation of the Yeast UBI4 Polyubiquitin Gene by Zap1 Transcription Factor via an Intragenic Promoter Is Critical for Zinc-deficient Growth

The Ubiquitin–Proteasome System of Saccharomyces cerevisiae

Blm10 Protein Promotes Proteasomal Substrate Turnover by an Active Gating Mechanism

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