Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy
Abstract
The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed.
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WDR5 is a highly conserved WD-40 repeat protein that plays a critical role in hematopoietic processes, regulating H3K4 methylation and HOX gene expression.
“WDR5 is a highly conserved WD-40 repeat protein that plays a critical role in hematopoietic processes, regulating H3K4 methylation and HOX gene expression.425,426”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [426]
Myc-WDR5 interaction is crucial for the control of cell proliferation, differentiation, and apoptosis through the regulation of gene expression.
“Myc-WDR5 interaction is crucial for the control of cell proliferation, differentiation, and apoptosis through the regulation of gene expression.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [426]
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- Authors
- Wang, Z.-H., Li, D.-D., Chen, W.-L., You, Q.-D., & Guo, X.-K.
- Venue
- Bioorganic & Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 26
- Issue
- 2
- Pages
- 356-365
- ISSN
- 0968-0896 (ISSN-L)
- OpenAlex
- W2773702346
- Cited by
- 16
- References
- 71
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 4
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioorganic & Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2015ZX09101032, 2017ZX09302003, 2017ZX0910004-003-006)
- China Pharmaceutical University (SKLNMZZCX201611)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- MLL1, protein-protein interaction, acute leukemia, H3K4 methylation, histone methyltransferase, homeobox genes, hematopoietic stem cell self-renewal, small molecule inhibitors, leukemia treatment, druggability
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Humans, Leukemia, Neoplasm Proteins, Protein Binding, Histone-Lysine N-Methyltransferase, Structure-Activity Relationship, Molecular Structure, Myeloid-Lymphoid Leukemia Protein
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