The University of Tokyo · 생화학·유전·분자생물학
Minoru Yoshida 교수의 연구실은 히스톤 디아세틸화 조절 메커니즘과 관련된 히스톤 디아세틸화효소(HDAC) 억제제의 기전 및 약리학적 작용을 중심으로 연구를 진행하고 있습니다. 특히 트리코스타틴 A(TSA)와 트라포크신(TPX)과 같은 마이크로벌 대사산물이 HDAC를 어떻게 억제하는지에 대한 분자 기전을 규명하며, 이는 암 치료 및 유전자 발현 조절의 새로운 전략을 제시하고자 합니다. 또한, 이들의 작용 기전을 기반으로 한 새로운 유형의 복합체 억제제를 합성하고, 이들의 작용이 가역성인지 여부를 분석함으로써 약물 설계에 응용하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
(R)-Trichostatin A (TSA) is a Streptomyces product which causes the induction of Friend cell differentiation and specific inhibition of the cell cycle of normal rat fibroblasts in the G1 and G2 phases at the very low concentrations. We found that TSA caused an accumulation of acetylated histone species in a variety of mammalian cell lines. Pulse-labeling experiments indicated that TSA markedly prolonged the in vivo half-life of the labile acetyl groups on histones in mouse mammary gland tumor ce
The genome of human T-cell leukemia virus (HTLV) was surveyed in fresh tumor cells of 163 patients with lymphoma and leukemia from the southwest part of Japan where adult T-cell leukemia (ATL) is endemic. Leukemic cells of all 88 cases of ATL tested so far were found to contain the provirus genome and also found to be monoclonal with respect to the integration site of provirus genome. In most cases of ATL, leukemic cells contained one or two copies of the complete HTLV provirus genome, and it wa
Reversible acetylation at the epsilon-amino group of lysines located at the conserved domain of core histones is supposed to play an important role in the regulation of chromatin structure and its transcriptional activity. One promising strategy for analyzing the precise function of histone acetylation is to block the activities of acetylating or deacetylating enzymes by specific inhibitors. Recently, two microbial metabolites, trichostatin A and trapoxin, were found to be potent inhibitors of h
Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs). TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group. On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid compound cyclic hydroxamic acid-containing peptide (
X-ray diffraction studies have been made of cubic (3C) and hexagonal (6H) polytypes of SiC under pressures to 105 and 95 GPa, respectively, using a diamond-anvil cell and an imaging plate technique. 3C-SiC undergoes a phase transition into the rocksalt-type structure at 100 GPa or higher accompanied by a volume reduction of 20.3%. The 6H polytype of SiC remains stable to the highest pressure studied, with a premonition of a phase transition above 90 GPa. Equation-of-state data for the two polyty
