ArticleCell cycle (Georgetown, Tex.)2016
MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- NSD proteins in anti-tumor immunity and their therapeutic targeting by protein degraders.Cellular and molecular life sciences : CMLS · 2025Review
- Conditional knockout of the NSD2 gene in mouse intestinal epithelial cells inhibits colorectal cancer progression.Animal models and experimental medicine · 2025Article
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment.Frontiers in immunology · 2022Article
- Deciphering cervical cancer-associated biomarkers by integrated multi-omics approach.American journal of translational research · 2022Article
- Review
- Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases.Experimental & molecular medicine · 2020Review
- The NSD2/WHSC1/MMSET methyltransferase prevents cellular senescence-associated epigenomic remodeling.Aging cell · 2020Article
- The Role of Methyltransferase NSD2 as a Potential Oncogene in Human Solid Tumors.OncoTargets and therapy · 2020Review
- The histone methyltransferase WHSC1 is regulated by EZH2 and is important for ovarian clear cell carcinoma cell proliferation.BMC cancer · 2019Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- MB4-2/MB4-3 transcripts ofOncotarget · 2017Article
- Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development.Cell reports · 2017Article
- AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis.The Journal of clinical investigation · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
The timely and precise duplication of cellular DNA is essential for maintaining genome integrity and is thus tightly-regulated. During mitosis and G1, the Origin Recognition Complex (ORC) binds to future replication origins, coordinating with multiple factors to load the minichromosome maintenance (MCM) complex onto future replication origins as part of the pre-replication complex (pre-RC). The pre-RC machinery, in turn, remains inactive until the subsequent S phase when it is required for replication fork formation, thereby initiating DNA replication. Multiple myeloma SET domain-containing protein (MMSET, a.k.a. WHSC1, NSD2) is a histone methyltransferase that is frequently overexpressed in aggressive cancers and is essential for normal human development. Several studies have suggested a role for MMSET in cell-cycle regulation; however, whether MMSET is itself regulated during cell-cycle progression has not been examined. In this study, we report that MMSET is degraded during S phase in a cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) and proteasome-dependent manner. Notably, we also report defects in DNA replication and a decreased association of pre-RC factors with chromatin in MMSET-depleted cells. Taken together, our results suggest a dynamic regulation of MMSET levels throughout the cell cycle, and further characterize the role of MMSET in DNA replication and cell-cycle progression.
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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.