• Bulletin of the Korean Chemical Society
• /
• v.33 no.6
• /
• pp.2063-2066
• /
• 2012

• BMB Reports
• /
• v.33 no.3
• /
• pp.263-267
• /
• 2000

We cloned $hda1^+$ (histone deacetylase 1) of fission yeast Schizosaccharomyces pombe. The hda1 of S. pombe was previously reported to encode for an active histone deacetylase (Rundlett et al., 1996; Olsson et al., 1998). The $hda1^+$ is phylogenetically related to the new open reading frame HOS2 of Saccharomyces cerevisiae and only shows a partial homology to the well-known histone deacetylase subclasses, RPD3 and HDA1. A single hda1 mRNA of 1.8 kb was detected at the same level in actively growing and nitrogen-starved cells. When highly over-expressed in S. pombe from an inducible promoter, $hda1^+$ inhibited cell proliferation and caused defects in morphology and cell division. The increased histone deacetylase activity was detected in hdar over-expressing cells. These results suggest that the Hda1p should function on the regulation of cell division possibly by (Allfrey, 1966) direct deacetylation of cytoskeletal (Wade et al., 1997) and cell division regulatory proteins, (Wolffe, 1997) or by controlling their gene expressions.

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2003.10a
• /
• pp.166-166
• /
• 2003

• BMB Reports
• /
• v.36 no.1
• /
• pp.110-119
• /
• 2003

The acetylation state of histone is reversibly regulated by histone acetyltransferase (HAT) and deacetylase (HDAC). An imbalance of this reaction leads to an aberrant behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, these key enzymes in the gene expression were cloned. They revealed a broad use of this modification, not only in histone, but also other proteins that involved transcription, nuclear transport, and cytoskeleton. These results suggest that HAT/HDAC takes charge of multiple-functions in the cell, not just the gene expression. HDAC is especially known to play an important role in carcinogenesis. The enzyme has been considered a target molecule for cancer therapy. The inhibition of HDAC activity by a specific inhibitor induces growth arrest, differentiation, and apoptosis of transformed or several cancer cells. Some of these inhibitors are in a clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy, and decipher the molecular mode of action for HDAC.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.184.1-184.1
• /
• 2003

HDAC and HAT (histone acetyltransferase) are involved in co-regulation in chromatin remodeling and the functional regulation of gene transcription. Abnormal recruitment of HDAC is related to carcinogenesis. Thus, the identification of potent histone deacetylase (HDAC) inhibitor has been considered as very intriguing approach for development for cancer chemotherapy. More recently, anti-inflammatory activity of SAHA cytokines was reported via reduction of proinflammatory cytokinres in vitro and in vivo. (omitted)

• Archives of Pharmacal Research
• /
• v.27 no.6
• /
• pp.640-645
• /
• 2004

Histone deacetylase inhibitors are new class of chemotherapeutic drugs able to induce tumor cell apoptosis and／or cell cycle arrest. Trichostatin A, an antifungal antibiotic, and HC-toxin are potent and specific inhibitors of histone deacetylase activity. In this study, we have examined the antiproliferative activities of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer, T47D cells. Both trichostatin A and HC-toxin showed potent antiprolifer-ative efficacy and cell cycle arrest at $G_2/M$ in T47D human breast cancer cells in a dose-dependent manner. Trichostatin A caused potent apoptosis of T47D human breast cancer cells and trichostatin A-induced apoptosis might be involved in an increase of caspase-3／7 activity. HC-toxin evoked apoptosis of T47D cells and HC-toxin induced apoptosis might not be medi-ated through direct increase in caspase-3/7 activity. We have identified potent activities of anti-proliferation, apoptosis, and cell cycle arrest of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer cell line T47D.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.166-166
• /
• 2003

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. The transcription of CYP3A4 is regulated by the Pregnenolone X receptor (PXR),of which human form is Steroid and Xenobiotics receptor (SXR).(omitted)

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.310.1-310.1
• /
• 2003

SD-2007 ia an apicidin analogue, possessing a potent histone deacetylase inhibiting activity. A rapid and senstive LC/MS method was developed for the determination of SD-2007 and its major active metabolite. apicidin. in rat serum. SD-2007 and apicidin was extracted by liquid-liquid extraction using methyl t-butyl ether. SD-2007 and apicidin were monitored in a SIM mode at m/z of 679 and 622, respectively. (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2001.11a
• /
• pp.110-110
• /
• 2001

Histone deacetylase(HDAC), a neuclear enzyme that regulates gene trascription and the assembly of newly synthesized chromatin, has received much attention in recent literature. The explosion of activity in this field has yielded the cloning of a mammalian gene which encodes a complementary histone acetyl trasferases. Several cyclic tetrapeptide inhibitors of HDAC has been reported to affect the hyperacetylation of mammalian and plant histones. Apicidin, a natural product HDAC inhibitor recently isolated at Merck Research Laboratories, induces therapeutic applications as a broad spectrum antiprotozoal agent to multi-drug resistant malaria and a potential antitumor agnet. The biological activity of apicidin appears to be attributable to inhibition of apicocomplexan HDAC at low nanomolar concentrations.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.168-168
• /
• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis.(omitted)