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| Status |
Public on Nov 24, 2016 |
| Title |
A Curcumin-Based CBP HAT Inhibitor Modulates the Transcription Functions of Tumor Suppressor p53 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Coactivator CREB-binding protein (CBP) regulates the transcription program of p53, which orchestrates cellular responses to a wide-range of stress conditions that cause genomic instability. Given the ability of CBP to regulate transcription by multiple mechanisms, the biological significance of its acetylation-directed functions may not be fully clear. The present study demonstrates the development of a curcumin-derived modulator of CBP histone acetyl-transferase (HAT) activity, CM354, which inhibits acetylation of p53 on lysine 382, acetylation of histone H3K27 and autoacetylation of CBP. These epigenetic changes are concomitant with downregulation of p53 and CBP functions, which facilitate the presence of histone methyl transferase, Enhancer of zeste homolog 2 (EZH2), on CDKNI1A/p21 promoter, thereby, enhancing the level of trimethylation on H3K27. Treatment with CM354 results in the activation of PARP and the abrogation of cellular growth. Genome-wide network analysis depicts that CM354 could alter cell-fate by enrichment of chromatin H3K27 methylation and activation of the polycomb group of proteins. Though previously reported HAT inhibitors act at higher concentrations and lack cell permeability, the present study shows the impact of modulating endogenous CBP HAT activity on chromatin landscape and p53 functions.
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| Overall design |
Gene expression in human U2OS cell lines after treatment of CM354 (1.5uM), Doxorubicin (300ng/ml), the combination of the two drugs, as well as the untreated control was measured. Each condition is performed in duplicates.
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| Contributor(s) |
Ma'ayan A, Mujtaba S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 23, 2016 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Zichen Wang |
| E-mail(s) |
zichen.wang@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Pharmacological Sciences
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| Lab |
Avi Ma'ayan
|
| Street address |
1468 Madison Ave
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA354786 |
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