Cited by 16Acute Myeloid Leukemia ResearchProtein Degradation and InhibitorsChromatin Remodeling and Cancer

Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy

Wang, Zhi-Hui, Li, Dong-Dong, Chen, Wei-Lin, You, Qi-Dong, Guo, Xiao-Ke·2018·Bioorganic & Medicinal Chemistry

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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Crossref · 10.1016/j.bmc.2017.11.045

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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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