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Updated: May 5, 2026
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
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A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly
M Koegl1, T Hoppe, S Schlenker
1Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
Cell
|March 25, 1999
Summary
A novel protein, E4, is essential for efficient multiubiquitination and proteasomal targeting. This ubiquitin chain assembly factor is crucial for cell survival under stress, highlighting its role in eukaryotic proteolysis.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Proteasomal degradation relies on multiubiquitin chains.
- Ubiquitination involves ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3).
Purpose of the Study:
- To identify factors involved in efficient multiubiquitination for proteasomal targeting.
- To characterize the function and family of a novel conjugation factor, E4.
Main Methods:
- Investigated multiubiquitination of a model substrate.
- Identified and characterized the E4 protein (UFD2 in yeast).
- Analyzed E4's role in ubiquitin chain assembly with E1, E2, and E3.
Main Results:
- Efficient multiubiquitination requires an additional factor, E4.
- E4 binds to ubiquitin moieties of preformed conjugates, catalyzing chain assembly.
- E4 defines a novel protein family with human and Dictyostelium members.
Conclusions:
- E4 is a crucial component for proteasomal substrate targeting.
- E4-dependent proteolysis pathways are utilized for diverse cellular functions, including stress survival.
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