Tohoku University · Medicine
Professor Hitoshi Shirakawa's research lab specializes in molecular and cellular biology, with a focus on chromatin-associated proteins, nuclear dynamics, and the regulation of gene expression. The lab investigates high mobility group (HMG) proteins such as HMG14/17 and novel nuclear factors like NBP-45, exploring their roles in chromatin remodeling, transcriptional activation, and embryonic development. Additionally, the lab examines the neuroprotective and anti-inflammatory effects of isoprenoids—particularly menaquinone-4 (MK-4) and geranylgeraniol (GGOH)—in microglial cells and neuroinflammatory disorders, linking cellular metabolism to neurological function and disease. These studies integrate molecular cloning, gene regulation, and neuroimmunology to uncover novel therapeutic targets for neurodegenerative and inflammatory diseases.
Figures are computed from collected data and may differ slightly.
The isolation and sequencing of a cDNA clone for the entire sequence of pig thymus non-histone protein HMG2 are described. cDNA the size of 1153 nucleotides contains an open reading frame of 627 nucleotides. The 5'-untranslated region of 146 nucleotides is extremely rich in GC residues whereas the 3'-untranslated region of 380 nucleotides is rich in AT residues. The open reading frame encodes 209 amino acids, which contain a unique continuous run of 23 acidic amino acids at the C-terminal. The d
Here we characterize a novel murine nuclear protein, which we named NBP-45, that is related to the ubiquitous nuclear proteins HMG-14/-17, binds specifically to nucleosome core particles, and can function as a transcriptional activator. NBP-45 mRNA is expressed at low levels and in variable amounts in all mouse tissues tested but is especially abundant in RNA extracted from 7-day-old mouse embryos, suggesting that it functions in early embryonic development. NBP-45 is composed of 406 amino acids
The overactivation of microglia is known to trigger inflammatory reactions in the central nervous system, which ultimately induce neuroinflammatory disorders including Alzheimer's disease. However, increasing evidence has shown that menaquinone-4 (MK-4), a subtype of vitamin K<sub>2</sub>, can attenuate inflammation in the peripheral system. Whereas it was also observed at high levels within the brain, its function in this organ has not been well characterized. Therefore, we investigated the eff
Chromosomal proteins high mobility group (HMG)-14 and HMG-17 are nucleosomal-binding proteins that unfold the chromatin fiber and enhance transcription from chromatin templates. Their intracellular organization is dynamic and related to both cell cycle and transcription. Here we examine possible mechanisms for targeting HMG-14/-17 to specific regions in chromatin. Chromatin immunoprecipitation assays indicate that HMG-17 protein is not preferentially associated with chromatin regions containing
Isoprenoids play widely differing roles in various physiological processes in animals and plants. Geranylgeraniol (GGOH) is an isoprenoid found in plants, and is an important metabolic derivative in the isoprenoid/cholesterol synthesis pathway. Earlier studies focused on GGOH's ability to improve the side effects of bisphosphonate therapy by regulating the mevalonate pathway. More recently, the mevalonate pathway-independent effects of GGOH have been described, including anti-inflammatory, anti-
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