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Polyisoprenylated Benzophenone, Garcinol, a Natural Histone Acetyltransferase Inhibitor, Represses Chromatin Transcription and Alters Global Gene Expression
Open accessAbstract
Histone acetylation is a diagnostic feature of transcriptionally active genes. The proper recruitment and function of histone acetyltransferases (HATs) and deacetylases (HDACs) are key regulatory steps for gene expression and cell cycle. Functional defects of either of these enzymes may lead to several diseases, including cancer. HATs and HDACs thus are potential therapeutic targets. Here we report that garcinol, a polyisoprenylated benzophenone derivative from Garcinia indica fruit rind, is a potent inhibitor of histone acetyltransferases p300 (IC50 approximately 7 microm) and PCAF (IC50 approximately 5 microm) both in vitro and in vivo. The kinetic analysis shows that it is a mixed type of inhibitor with an increased affinity for PCAF compared with p300. HAT activity-dependent chromatin transcription was strongly inhibited by garcinol, whereas transcription from DNA template was not affected. Furthermore, it was found to be a potent inducer of apoptosis, and it alters (predominantly down-regulates) the global gene expression in HeLa cells.
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Hung, H.-L., Lau, J., Kim, A. Y., Weiss, M. J., & Blobel, G. A. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3496 · Cited by 247
An, W., Palhan, V. B., Karymov, M. A., Leuba, S. H., & Roeder, R. G. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00497-5 · Cited by 100
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Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours
Lasko, L. M., Jakob, C. G., Edalji, R. P., Qiu, W., Montgomery, D., Digiammarino, E. L., Hansen, T. M., Risi, R. M., Frey, R., Manaves, V., et al. (2017) · Nature · doi:10.1038/nature24028 · Cited by 858
Morimoto, T., Sunagawa, Y., Kawamura, T., Takaya, T., Wada, H., Nagasawa, A., Komeda, M., Fujita, M., Shimatsu, A., Kita, T., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33160 · Cited by 423
Balmer, M. L., Ma, E. H., Bantug, G. R., Grählert, J., Pfister, S., Glatter, T., Jauch, A., Dimeloe, S., Slack, E., Dehio, P., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.03.016 · Cited by 361
Spermidine induces autophagy by inhibiting the acetyltransferase EP300
Pietrocola, F., Lachkar, S., Enot, D. P., Niso-Santano, M., Bravo-San Pedro, J. M., Sica, V, Izzo, V, Maiuri, M. C., Madeo, F., Mariño, G., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.215 · Cited by 357
Metadata
- Authors
- Balasubramanyam, K., Altaf, M., Varier, R. A., Swaminathan, V., Ravindran, A., Sadhale, P. P., & Kundu, T. K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 279
- Issue
- 32
- Pages
- 33716-33726
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2015052870
- Cited by
- 546
- References
- 2
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Balasubramanyam, K., Altaf, M., Varier, R. A., Swaminathan, V., Ravindran, A., Sadhale, P. P., & Kundu, T. K. (2004). Polyisoprenylated Benzophenone, Garcinol, a Natural Histone Acetyltransferase Inhibitor, Represses Chromatin Transcription and Alters Global Gene Expression. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m402839200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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