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A novel, universally active C-terminal protein degradation signal generated by alternative splicing

Peter, Stephen A. and Isaac, Jessica S. and Narberhaus, Franz and Weigand, Julia E. (2021):
A novel, universally active C-terminal protein degradation signal generated by alternative splicing.
In: Journal of molecular biology, 433 (8), p. 166890. Elsevier, ISSN 1089-8638,
DOI: 10.1016/j.jmb.2021.166890,
[Article]

Abstract

Proteome integrity is crucial for cellular homeostasis and adaptation to stress conditions such as hypoxia. One mechanism for rapid adaptation of the proteome in response to changing environmental signals is alternative splicing. In addition to generating different protein isoforms, alternative splicing is also capable of controlling total protein levels by the regulated synthesis of non-productive mRNA isoforms. The hypoxia-induced isoform E of the tumor suppressor MAX is produced by retention and translation of the last intron. This leads to an alternative C-terminus that harbors a potent C-degron, the isoE degron. Strikingly, the isoE degron represents a universal protein degradation signal that is not only functional in mammalian cells, but also in yeast and even in bacteria. Essential for efficient protein decay is a conserved (F/W)xxW motif. Degradation of isoE tagged proteins is mediated by the proteasome in eukaryotes and Lon protease in bacteria. Thus, the isoE degron is a broadly applicable and highly efficient tool in protein analyses.

Item Type: Article
Erschienen: 2021
Creators: Peter, Stephen A. and Isaac, Jessica S. and Narberhaus, Franz and Weigand, Julia E.
Title: A novel, universally active C-terminal protein degradation signal generated by alternative splicing
Language: English
Abstract:

Proteome integrity is crucial for cellular homeostasis and adaptation to stress conditions such as hypoxia. One mechanism for rapid adaptation of the proteome in response to changing environmental signals is alternative splicing. In addition to generating different protein isoforms, alternative splicing is also capable of controlling total protein levels by the regulated synthesis of non-productive mRNA isoforms. The hypoxia-induced isoform E of the tumor suppressor MAX is produced by retention and translation of the last intron. This leads to an alternative C-terminus that harbors a potent C-degron, the isoE degron. Strikingly, the isoE degron represents a universal protein degradation signal that is not only functional in mammalian cells, but also in yeast and even in bacteria. Essential for efficient protein decay is a conserved (F/W)xxW motif. Degradation of isoE tagged proteins is mediated by the proteasome in eukaryotes and Lon protease in bacteria. Thus, the isoE degron is a broadly applicable and highly efficient tool in protein analyses.

Journal or Publication Title: Journal of molecular biology
Journal volume: 433
Number: 8
Publisher: Elsevier
Divisions: 10 Department of Biology
10 Department of Biology > RNA Biochemistry
Date Deposited: 05 Mar 2021 08:49
DOI: 10.1016/j.jmb.2021.166890
Identification Number: pmid:33636164
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