ArticleThe Journal of biological chemistry2013
Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression and E2F1-responsive gene expression via association with host cell factor-1 (HCF-1).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.Science translational medicine · 2024Pooled it
- A SET domain-containing protein and HCF-1 maintain transgenerational epigenetic memory.Nature communications · 2026Article
- Epigenetic co-regulator HCF-1 promotes lung cancer via O-GlcNAcylation-dependent pathways.Molecular therapy. Oncology · 2025Article
- Comprehensive genome annotation of the model ciliate Tetrahymena thermophila by in-depth epigenetic and transcriptomic profiling.Nucleic acids research · 2025Article
- SUMO-mediated regulation of H3K4me3 reader SET-26 controls germline development in C. elegans.PLoS biology · 2025Article
- CanPharmaceuticals (Basel, Switzerland) · 2024Review
- Defining Biological and Biochemical Functions of Noncanonical SET Domain Proteins.Journal of molecular biology · 2024Review
- The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation in C. elegans.Nature communications · 2024Article
- Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Upregulation of HCFC1 expression promoted hepatocellular carcinoma progression through inhibiting cell cycle arrest and correlated with immune infiltration.Journal of Cancer · 2023Article
- ASXL1/2 mutations and myeloid malignancies.Journal of hematology & oncology · 2022Review
- MLL5 is involved in retinal photoreceptor maturation through facilitating CRX-mediated photoreceptor gene transactivation.iScience · 2022Article
- SETD5 modulates homeostasis of hematopoietic stem cells by mediating RNA Polymerase II pausing in cooperation with HCF-1.Leukemia · 2022Article
- Review
- O-GlcNAcylation links oncogenic signals and cancer epigenetics.Discover oncology · 2021Review
- Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549.Oncology letters · 2021Article
- Article
- MLL5, a histone modifying enzyme, regulates androgen receptor activity in prostate cancer cells by recruiting co-regulators, HCF1 and SET1.BMB reports · 2020Article
- HCF-1 promotes cell cycle progression by regulating the expression of CDC42.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trithorax group proteins methylate lysine 4 of histone 3 (H3K4) at active gene promoters. MLL5 protein, a member of the Trithorax protein family, has been implicated in the control of the cell cycle progression; however, the underlying molecular mechanism(s) have not been fully determined. In this study, we found that the MLL5 protein can associate with the cell cycle regulator "host cell factor" (HCF-1). The interaction between MLL5 and HCF-1 is mediated by the "HCF-1 binding motif" (HBM) of the MLL5 protein and the Kelch domain of the HCF-1 protein. Confocal microscopy showed that the MLL5 protein largely colocalized with HCF-1 in the nucleus. Knockdown of MLL5 resulted in reduced cell proliferation and cell cycle arrest in the G1 phase. Moreover, down-regulation of E2F1 target gene expression and decreased H3K4me3 levels at E2F1-responsive promoters were observed in MLL5 knockdown cells. Additionally, the core subunits, including ASH2L, RBBP5, and WDR5, that are necessary for effective H3K4 methyltransferase activities of the Trithorax protein complexes, were absent in the MLL5 complex, suggesting that a distinct mechanism may be used by MLL5 for exerting its H3K4 methyltransferase activity. Together, our findings demonstrate that MLL5 could associate with HCF-1 and then be recruited to E2F1-responsive promoters to stimulate H3K4 trimethylation and transcriptional activation, thereby facilitating the cell cycle G1 to S phase transition.
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