ArticleMolecular and cellular biology2009
Masking of a nuclear signal motif by monoubiquitination leads to mislocalization and degradation of the regulatory enzyme cytidylyltransferase.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 57 citations in OpenAlex.
- Biosynthesis of Phosphatidylethanolamine and Phosphatidylcholine via the Kennedy Pathway in Cancer and Other Pathological Conditions.International journal of molecular sciences · 2026Review
- Membrane curvature elastic stress triggers recruitment of PML-II onto the inner nuclear membrane.Molecular biology of the cell · 2026Article
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Differential contributions of phosphotransferases CEPT1 and CHPT1 to phosphatidylcholine homeostasis and lipid droplet biogenesis.The Journal of biological chemistry · 2023Article
- Implications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease.Frontiers in molecular neuroscience · 2023Article
- Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- How Is the Fidelity of Proteins Ensured in Terms of Both Quality and Quantity at the Endoplasmic Reticulum? Mechanistic Insights into E3 Ubiquitin Ligases.International journal of molecular sciences · 2021Review
- Chemical inhibition of FBXO7 reduces inflammation and confers neuroprotection by stabilizing the mitochondrial kinase PINK1.JCI insight · 2020Article
- Cell-to-cell transmission of C9orf72 poly-(Gly-Ala) triggers key features of ALS/FTD.The EMBO journal · 2020Article
- Resolving the Complexity of Ubiquitin Networks.Frontiers in molecular biosciences · 2020Review
- Patrolling the nucleus: inner nuclear membrane-associated degradation.Current genetics · 2019Review
- Distribution of Proteins at the Inner Nuclear Membrane Is Regulated by the Asi1 E3 Ligase inGenetics · 2019Article
- Identification and characterization of ubiquitinylation sites in TAR DNA-binding protein of 43 kDa (TDP-43).The Journal of biological chemistry · 2018Article
- Post-translational modification of the interferon-gamma receptor alters its stability and signaling.The Biochemical journal · 2017Article
- IL-4 Induces IL17Rb Gene Transcription in Monocytic Cells with Coordinate Autocrine IL-25 Signaling.American journal of respiratory cell and molecular biology · 2017Article
- SCFThe Journal of biological chemistry · 2017Article
- PTRF/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges.eLife · 2016Article
- Degradation of oxidized proteins by the proteasome: Distinguishing between the 20S, 26S, and immunoproteasome proteolytic pathways.Molecular aspects of medicine · 2016Review
- Cleavage of Signal Regulatory Protein α (SIRPα) Enhances Inflammatory Signaling.The Journal of biological chemistry · 2015Article
- Nuclear-localized CTP:phosphocholine cytidylyltransferase α regulates phosphatidylcholine synthesis required for lipid droplet biogenesis.Molecular biology of the cell · 2015Article
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Monoubiquitination aids in the nuclear export and entrance of proteins into the lysosomal degradative pathway, although the mechanisms are unknown. Cytidylyltransferase (CCTalpha) is a proteolytically sensitive lipogenic enzyme containing an NH(2)-terminal nuclear localization signal (NLS). We show here that CCTalpha is monoubiquitinated at a molecular site (K(57)) juxtaposed near its NLS, resulting in disruption of its interaction with importin-alpha, nuclear exclusion, and subsequent degradation within the lysosome. Cellular expression of a CCTalpha-ubiquitin fusion protein that mimics the monoubiquitinated enzyme resulted in cytoplasmic retention. A CCTalpha K(57R) mutant exhibited an extended half-life, was retained in the nucleus, and displayed proteolytic resistance. Importantly, by using CCTalpha-ubiquitin hybrid constructs that vary in the intermolecular distance between ubiquitin and the NLS, we show that CCTalpha monoubiquitination masks its NLS, resulting in cytoplasmic retention. These results unravel a unique molecular mechanism whereby monoubiquitination governs the trafficking and life span of a critical regulatory enzyme in vivo.
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