Many proteins contain ubiquitin-binding domains or motifs (UBDs), such as the UIM (ubiquitin-interacting motif) and are referred to as ubiquitin receptors. Ubiquitin receptors themselves are frequently monoubiquitinated by a process that requires the presence of a UBD and is referred to as coupled monoubiquitination. Using a UIM-containing protein, eps15, as a model, we show here that coupled monoubiquitination strictly depends on the ability of the UIM to bind to monoubiquitin (mUb). We found that the underlying molecular mechanism is based on interaction between the UIM and a ubiquitin ligase (E3), which has itself been modified by ubiquitination. Furthermore, we demonstrate that the in vivo ubiquitination of members of the Nedd4 family of E3 ligases correlates with their ability to monoubiquitinate eps15. Thus, our results clarify the mechanism of coupled monoubiquitination and identify the ubiquitination of E3 ligases as a critical determinant in this process.
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http://dx.doi.org/10.1038/ncb1484 | DOI Listing |
Mol Cell
November 2024
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address:
Nat Commun
November 2024
Division of Biochemistry, Mannheim Institute for Innate Immunoscience (MI3) and Mannheim Cancer Center (MCC), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany.
Cell Rep
November 2024
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. Electronic address:
The Fanconi anemia (FA) pathway removes interstrand crosslinks (ICLs) between the Watson-Crick strands of the DNA double helix in humans. Central to the pathway is the FANCD2/FANCI complex, which must be loaded onto chromosomes. Here, we report the identification of a PP2A phosphatase complex, which specifically dephosphorylates an inhibitory cluster in FANCD2, thereby licensing its loading in response to DNA damage.
View Article and Find Full Text PDFJ Clin Invest
July 2024
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Nat Genet
June 2024
Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), Rome, Italy.
Chromatin modifications are linked with regulating patterns of gene expression, but their causal role and context-dependent impact on transcription remains unresolved. Here we develop a modular epigenome editing platform that programs nine key chromatin modifications, or combinations thereof, to precise loci in living cells. We couple this with single-cell readouts to systematically quantitate the magnitude and heterogeneity of transcriptional responses elicited by each specific chromatin modification.
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