The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Histone Deacetylase Is a Target of Valproic Acid-Mediated Cellular Differentiation
Open accessAbstract
Valproic acid (VPA), a well-established therapy for seizures and bipolar disorder, has recently been shown to inhibit histone deacetylases (HDACs). Similar to more widely studied HDAC inhibitors, VPA can cause growth arrest and induce differentiation of transformed cells in culture. Whether this effect of VPA is through inhibition of HDACs or modulation of another target of VPA has not been tested. We have used a series of VPA analogs to establish a pharmacological profile for HDAC inhibition. We find that VPA and its analogs inhibit multiple HDACs from class I and class II (but not HDAC6 or HDAC10) with a characteristic order of potency in vitro. These analogs also induce hyperacetylation of core histones H3 and H4 in intact cells with an order of potency that parallels in vitro inhibition. VPA and VPA analogs induce differentiation in hematopoietic cell lines in a p21-dependent manner, and the order of potency for induction of differentiation parallels the potencies for inhibition in vitro, as well as for acetylation of histones associated with the p21 promoter, supporting the argument that differentiation caused by VPA is mediated through inhibition of HDACs. These findings provide additional evidence that VPA, a well-tolerated, orally administered drug with extensive clinical experience, may serve as an effective chemotherapeutic agent through targeting of HDACs.
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Cites
The language of covalent histone modifications
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HDAC6 is a microtubule-associated deacetylase
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Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
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Histone deacetylases and cancer: causes and therapies
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Self-citationRichon, V. M., Sandhoff, T. W., Rifkind, R. A., & Marks, P. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.180316197 · Cited by 1,090
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Histone deacetylase inhibitors as new cancer drugs
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Cited by
Multiple roles of HDAC inhibition in neurodegenerative conditions
Chuang, D.-M., Leng, Y., Marinova, Z., Kim, H.-J., & Chiu, C.-T. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.06.002 · Cited by 676
Wilson, A. J., Byun, D.-S., Popova, N., Murray, L. B., L'Italien, K., Sowa, Y., Arango, D., Velcich, A., Augenlicht, L. H., & Mariadason, J. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510023200 · Cited by 575
Therapeutic potential of mood stabilizers lithium and valproic acid:Beyond bipolar disorder
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Retinoic acid receptors: From molecular mechanisms to cancer therapy
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HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination
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Metadata
- Authors
- Gurvich, N., Tsygankova, O. M., Meinkoth, J. L., & Klein, P. S.
- Venue
- Cancer Research
- Published
- 2004-02-01
- Volume
- 64
- Issue
- 3
- Pages
- 1079-1086
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2165455805
- Cited by
- 459
- References
- 31
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- bronze
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