ArticlePloS one2015
Mixed Lineage Leukemia 5 (MLL5) Protein Stability Is Cooperatively Regulated by O-GlcNac Transferase (OGT) and Ubiquitin Specific Protease 7 (USP7).
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Regenerative potential of von Hippel-Lindau tumor suppressor protein.World journal of biological chemistry · 2026Review
- Functional analysis of O-GlcNAcylation by networking of OGT interactors and substrates.Nature chemical biology · 2026Article
- The roles of OGT and its mechanisms in cancer.Cell & bioscience · 2024Review
- Unraveling the Immune Regulatory Functions of USP5: Implications for Disease Therapy.Biomolecules · 2024Review
- Defining Biological and Biochemical Functions of Noncanonical SET Domain Proteins.Journal of molecular biology · 2024Review
- O-GlcNAcylation: the sweet side of epigenetics.Epigenetics & chromatin · 2023Review
- Review
- β-Carotene enhances the expression of inflammation-related genes and histone H3 K9 acetylation, K4 dimethylation, and K36 trimethylation around these genes in juvenile macrophage-like THP-1 cells.Biochemistry and biophysics reports · 2022Article
- Spatial and temporal proteomics reveals the distinct distributions and dynamics of O-GlcNAcylated proteins.Cell reports · 2022Article
- MLL5 is involved in retinal photoreceptor maturation through facilitating CRX-mediated photoreceptor gene transactivation.iScience · 2022Article
- Splice variants denote differences between a cancer stem cell side population of EWSR1‑ERG‑based Ewing sarcoma cells, its main population and EWSR1‑FLI‑based cells.International journal of molecular medicine · 2022Article
- Review
- O-GlcNAcylation links oncogenic signals and cancer epigenetics.Discover oncology · 2021Review
- Phylogenomics Identifies an Ancestral Burst of Gene Duplications Predating the Diversification of Aphidomorpha.Molecular biology and evolution · 2020Article
- Review
- MLL5α activates AR/NDRG1 signaling to suppress prostate cancer progression.American journal of cancer research · 2020Article
- ROCK2 mediates osteosarcoma progression and TRAIL resistance by modulating O-GlcNAc transferase degradation.American journal of cancer research · 2020Article
- Article
- Blocked O-GlcNAc cycling disrupts mouse hematopoeitic stem cell maintenance and early T cell development.Scientific reports · 2019Article
- SET domains and stress: uncovering new functions for yeast Set4.Current genetics · 2019Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mixed lineage leukemia 5 (MLL5) protein is a trithorax family histone 3 lysine 4 (H3K4) methyltransferase that regulates diverse biological processes, including cell cycle progression, hematopoiesis and cancer. The mechanisms by which MLL5 protein stability is regulated have remained unclear to date. Here, we showed that MLL5 protein stability is cooperatively regulated by O-GlcNAc transferase (OGT) and ubiquitin-specific protease 7 (USP7). Depletion of OGT in cells led to a decrease in the MLL5 protein level through ubiquitin/proteasome-dependent proteolytic degradation, whereas ectopic expression of OGT protein suppressed MLL5 ubiquitylation. We further identified deubiquitinase USP7 as a novel MLL5-associated protein using mass spectrometry. USP7 stabilized the MLL5 protein through direct binding and deubiquitylation. Loss of USP7 induced degradation of MLL5 protein. Conversely, overexpression of USP7, but not a catalytically inactive USP7 mutant, led to decreased ubiquitylation and increased MLL5 stability. Co-immunoprecipitation and co-immunostaining assays revealed that MLL5, OGT and USP7 interact with each other to form a stable ternary complex that is predominantly located in the nucleus. In addition, upregulation of MLL5 expression was correlated with increased expression of OGT and USP7 in human primary cervical adenocarcinomas. Our results collectively reveal a novel molecular mechanism underlying regulation of MLL5 protein stability and provide new insights into the functional interplay among O-GlcNAc transferase, deubiquitinase and histone methyltransferase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.