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  3. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
  4. Volume 24, Issue 17
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Volume 24, Issue 17
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

Histone methyltransferase absent, small, or homeotic discs1-like () is composed of su(var)3-9, enhancer of zeste, trithorax (SET) domain, pleckstrin homology domain (PHD) domain, middle (MID) domain, and bromo adjacent homology (BAH) domain. The SET domain of is known to mediate mediate H3K36 dimethylation (H3K36me2) modification. However, the specific functions of the PHD-BAH domain remain largely unexplored. This study aimed to explore the biological function of the PHD-BAH domain in .

Methods

We employed a range of techniques, including a prokaryotic fusion protein expression purification system, pull-down assay, Isothermal Titration Calorimetry (ITC), polymerase chain reaction (PCR), and site-directed mutagenesis, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-Cas9) gene editing, cell culture experiment, western blot, cell proliferation assay, and cell apoptosis test.

Results

The PHD-BAH domain in preferentially binds to the H3K4me2 peptide over H3K4 monomethylation (H3K4me1) and H3K4 trimethylation (H3K4me3) peptide. Notably, the W2603A mutation within the PHD-BAH domain could disrupt the interaction with H3K4me2 Compared with wild-type Cholangiocarcinoma (CHOL) cells, deletion of the PHD-BAH domain in led to increased CHOL cell apoptosis and reduced cell proliferation ( < 0.001). Additionally, the W2603A mutation affected the regulation of the proteasome 20S subunit beta (PSMB) family gene set.

Conclusion

W2603A mutation was crucial for the interaction between the PHD-BAH domain and the H3K4me2 peptide. regulated CHOL cell survival and proliferation through its PHD-BAH domain by modulating the expression of the family gene set.

© 2024 Bentham Science Publishers
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2024-10-01
2025-04-22

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PHD-BAH Domain in ASH1L Could Recognize H3K4 Methylation and Regulate the Malignant Behavior of Cholangiocarcinoma
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 24, 1264 (2024); https://doi.org/10.2174/0118715206312004240712072532
/content/journals/acamc/10.2174/0118715206312004240712072532
/content/journals/acamc/10.2174/0118715206312004240712072532
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  • Article Type:     Research Article
Keyword(s): ASH1L; CHOL cancer; H3K4me2 peptide; PHD-BAH domain; PSMB family genes; W2603A mutation

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