Evidence map›Paper›PMID 18708352›Full record

ArticleThe Journal of biological chemistry2008

Amino acids induce peptide uptake via accelerated degradation of CUP9, the transcriptional repressor of the PTR2 peptide transporter.

Zanxian Xia, Glenn C Turner, Cheol-Sang Hwang, Christopher Byrd, Alexander Varshavsky

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. The Antipsychotic Drug Clozapine Suppresses the RGS4 Polyubiquitylation and Proteasomal Degradation Mediated by the Arg/N-Degron Pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021
    Article
  4. Article
  5. Five enzymes of the Arg/N-degron pathway form a targeting complex: The concept of superchanneling.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  6. Transport Deficiency Is the Molecular Basis ofFrontiers in microbiology · 2017
    Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. The N-end rule pathway.Annual review of biochemistry · 2012
    Review
  20. The N-end rule pathway and regulation by proteolysis.Protein science : a publication of the Protein Society · 2011
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Zanxian XiaDivision of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Glenn C Turner
Cheol-Sang Hwang
Christopher Byrd
Alexander Varshavsky
California Institute of Technology · USCold Spring Harbor Laboratory · USWilson Sonsini Goodrich & Rosati · US

Funding

The Functions, Mechanisms, and Regulation of N-Terminal ArginylationR01GM031530 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ALEXANDER J VARSHAVSKY · 1985 to 2026
$14.5M
Ubiquitin Ligases, Mechanisms and Functions of the N-End Rule PathwayR01DK039520 · NIDDK · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VARSHAVSKY, ALEXANDER J · 1988 to 2025
$10.0M
MECHANICS AND FUNCTIONS OF THE N-END RULE PATHWAYR37DK039520 · NIDDK · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI VARSHAVSKY, ALEXANDER J · 1998 to 2007
$4.4M
Ubiquitin Ligases, Mechanisms and Functions of the N-End Rule PathwayR56DK039520 · NIDDK · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI VARSHAVSKY, ALEXANDER J · 2008 to 2008
$161k
NIDDK NIH HHS DK39520NIDDK NIH HHS R01 DK039520NIGMS NIH HHS GM31530NIGMS NIH HHS R01 GM031530
6 · The paper itself

Abstract

Multiple pathways link expression of PTR2, the transporter of di- and tripeptides in the yeast Saccharomyces cerevisiae, to the availability and quality of nitrogen sources. Previous work has shown that induction of PTR2 by extracellular amino acids requires, in particular, SSY1 and PTR3. SSY1 is structurally similar to amino acid transporters but functions as a sensor of amino acids. PTR3 acts downstream of SSY1. Expression of the PTR2 peptide transporter is induced not only by amino acids but also by dipeptides with destabilizing N-terminal residues. These dipeptides bind to UBR1, the ubiquitin ligase of the N-end rule pathway, and allosterically accelerate the UBR1-dependent degradation of CUP9, a transcriptional repressor of PTR2. UBR1 targets CUP9 through its internal degron. Here we demonstrate that the repression of PTR2 by CUP9 requires TUP1 and SSN6, the corepressor proteins that form a complex with CUP9. We also show that the induction of PTR2 by amino acids is mediated by the UBR1-dependent acceleration of CUP9 degradation that requires both SSY1 and PTR3. The acceleration of CUP9 degradation is shown to be attained without increasing the activity of the N-end rule pathway toward substrates with destabilizing N-terminal residues. We also found that GAP1, a general amino acid transporter, strongly contributes to the induction of PTR2 by Trp. Although several aspects of this complex circuit remain to be understood, our findings establish new functional links between the amino acids-sensing SPS system, the CUP9-TUP1-SSN6 repressor complex, the PTR2 peptide transporter, and the UBR1-dependent N-end rule pathway.

Indexed as

Transcription, GeneticAllosteric SiteAmino AcidsBiological TransportCarrier ProteinsDNA-Binding ProteinsHomeodomain ProteinsIntracellular Signaling Peptides and ProteinsMembrane ProteinsMembrane Transport ProteinsModels, BiologicalModels, GeneticNuclear ProteinsProtein Structure, TertiaryRepressor ProteinsSaccharomyces cerevisiaeAmino AcidsCarrier ProteinsCUP9 protein, S cerevisiaeCYC8 protein, S cerevisiaeDNA-Binding ProteinsHomeodomain ProteinsIntracellular Signaling Peptides and ProteinsMembrane ProteinsMembrane Transport ProteinsNuclear ProteinsPTR2 protein, S cerevisiaePTR3 protein, S cerevisiaeRepressor ProteinsSaccharomyces cerevisiae ProteinsSSY1 protein, S cerevisiaeTranscription FactorsTUP1 protein, S cerevisiaeUbiquitin-Protein LigasesUBR1 protein, S cerevisiae

Identifiers

PMID18708352
PMCPMC2570885
OpenAlexW2143038903

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.