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The Arg/N-degron pathway targets transcription factors and regulates specific genes

Authors: Tri T. M. Vu; Dylan C. Mitchell; Steven P. Gygi; Alexander Varshavsky;

The Arg/N-degron pathway targets transcription factors and regulates specific genes

Abstract

Significance The Arg/N-degron pathway targets proteins for degradation by recognizing their N-terminal or internal degradation signals. In the present study, we compared wild-type human cells to their double-knockout (2-KO) counterparts that lacked the UBR1/UBR2 ubiquitin ligases of the Arg/N-degron pathway. We found that a number of specific genes were either strongly induced or strongly repressed in 2-KO cells. In addition, specific transcription factors, including glucocorticoid receptor, were identified here as physiological substrates of the Arg/N-degron pathway. We discuss the emerged role of this proteolytic system as a regulator of mammalian gene expression.

Related Organizations
Keywords

PREP1, Monocarboxylic Acid Transporters, 570, Intermediate Filaments, UBR1, Mass Spectrometry, Gene Knockout Techniques, Receptors, Glucocorticoid, Antigens, Neoplasm, Humans, RNA-Seq, Eye Proteins, degradation, Homeodomain Proteins, Activating Transcription Factor 3, Microfilament Proteins, Neoplasm Proteins, GR, HEK293 Cells, Gene Expression Regulation, Proteolysis, Receptors, Adrenergic, beta-2, transcription, Protein Binding, Signal Transduction, Transcription Factors

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    15
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
15
Top 10%
Average
Top 10%
Green
bronze