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Koichiro Kako

Bio: Koichiro Kako is an academic researcher from University of Tsukuba. The author has contributed to research in topics: Arginine & Methylation. The author has an hindex of 14, co-authored 35 publications receiving 1203 citations. Previous affiliations of Koichiro Kako include National Institute of Advanced Industrial Science and Technology.

Papers
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TL;DR: PRMT1 knockdown led to a decrease in oxidative-stress-induced apoptosis depending on the PI3K-Akt signaling pathway, and predicted a role for arginine methylation as an inhibitory modification against Akt-mediated phosphorylation.

390 citations

Journal ArticleDOI
TL;DR: Two-dimensional phosphopeptide mapping using mutation of phosphorylation sites for MAPK revealed that the nine serine residues in Foxo1 are specifically phosphorylated by Erk and p38, and that this phosphorylations regulates the function of Foxo 1 as a coactivator for Ets-1.

215 citations

Journal ArticleDOI
TL;DR: It was found that the activity of lactate dehydrogenase was also normal in E6.5 embryos, implying that the activation of CCO by Cox17p may not be essential to the progress of embryogenesis before gastrulation.
Abstract: Copper is an essential trace element for aerobic organisms, acting as a cofactor for mitochondrial, cytosolic, and vesicular enzymes (27). In the past few years, three independent pathways for intracellular copper trafficking have been identified in yeast. Generally, copper in the form of Cu(I) is transported across the plasma membrane by the high-affinity Cu transporter Ctr1 and is then picked up and transported to each target organelle by cytosolic small proteins (18). Cox17p is one of these small proteins and is considered to be involved in copper recruitment to mitochondria and in the functional assembly of cytochrome c oxidase (CCO), the terminal enzyme of the mitochondrial respiratory chain (5, 6). It was reported that a proline-rich 62-mer polypeptide was purified from the gel filtration fraction of a porcine heart extract (26). A structural analysis showed that it was a mammalian homologue of yeast Cox17p (yCox17p). Along with the porcine protein (4, 26), human (1), rat (12), and mouse (12, 17) Cox17p homologues have been identified to date. Although it was thought that yCox17p forms a homooligomer (8) and guides Cu to mitochondria for incorporation into CCO, its physiological role in mammals is unclear. Recently, it was reported that expression levels of Cox17p mRNA were high in the mouse heart, kidneys, and brain as well as in some endocrine cell lines but quite low in the small intestine, liver, and some fibroblast cell lines (12). Furthermore, COX17 genomic DNA has been isolated, and its genetic structure and the 5′-promoter function were determinated. Mouse COX17 is a single gene that spans ∼6 kb, consists of three exons, and is mapped to the center of chromosome 16 (25). Transcription factors Sp1 and NRF-1 (nuclear respiration factor 1) drive the basal transcription of this gene (24). The transcriptional mechanism of COX17 is similar to that of other COX subunits (21), which indirectly implies that the Cox17p is also involved in cellular respiration. Since our goal is to determine the physiological function of Cox17p in the mammalian system, we first examined the copper-binding activity of mammalian Cox17p in vitro and then generated mice carrying a null mutation of COX17 and analyzed them. Next, we present genetic evidence that COX17 is required for the transport of copper to the mitochondria and CCO activity. Several case of specific deficiencies of CCO in humans have been reported, with most of them being associated with severe neonatal or infantile lactic acidosis and early death. For example, patients with a fatal cardioencephalomyopathy or hypertrophic cardiomyopathy, marked by a severe CCO deficiency, harbor mutations in the SCO2 gene, which is a related CCO assembly gene that is thought to cooperate with Cox17p (10, 11, 20). A COX17-deficient mouse underwent embryonic death with severe reduction in CCO activity, which is consistent with the previous clinical evidence as in the case of the SCO2 mutation. Furthermore, we show here that Cox17p is not only indispensable for the activation of CCO but also essential for embryonic growth and development. We also report a marked reduction in CCO activity in 6.5-day viable embryos (E6.5), indicating that CCO-independent embryogenesis progressed up to this stage. Most recently, gene disruption of Ctr1 was also reported to result in embryonic death (13, 14). The relationship between this molecule and Cox17p is also discussed in light of the developmental mechanism.

106 citations

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TL;DR: It is demonstrated that the estrogen receptor β (ERβ) mediates inhibition by the antiestrogen ICI 182,780 (ICI) and its enhancement by estrogen, and affects prostate tumor growth through ERβ-mediated regulation of KLF5.
Abstract: Clinical evidence suggests that antiestrogens inhibit the development of androgen-insensitive prostate cancer. Here, we show that the estrogen receptor β (ERβ) mediates inhibition by the antiestrogen ICI 182,780 (ICI) and its enhancement by estrogen. ERβ associated with gene promoters through the tumor-suppressing transcription factor KLF5 (Kruppel-like zinc finger transcription factor 5). ICI treatment increased the recruitment of the transcription coactivator CBP [CREB (adenosine 3',5'-monophosphate response element-binding protein)-binding protein] to the promoter of FOXO1 through ERβ and KLF5, which enhanced the transcription of FOXO1. The increase in FOXO1 abundance led to anoikis in prostate cancer cells, thereby suppressing tumor growth. In contrast, estrogen induced the formation of complexes containing ERβ, KLF5, and the ubiquitin ligase WWP1 (WW domain containing E3 ubiquitin protein ligase 1), resulting in the ubiquitination and degradation of KLF5. The combined presence of KLF5 and ERβ positively correlated with longer cancer-specific survival in prostate cancer patients. Our results demonstrate that estrogens and antiestrogens affect prostate tumor growth through ERβ-mediated regulation of KLF5.

96 citations

Journal ArticleDOI
TL;DR: It is shown that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans and biochemical analyses indicate that PRMT-1 methylates DAF-16, thereby blocking its phosphorylation by AKT.

71 citations


Cited by
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TL;DR: This work provides a broad overview of how histone methylation is regulated and leads to biological outcomes and suggests its links to disease and ageing and possibly to transmission of traits across generations are illustrated.
Abstract: Organisms require an appropriate balance of stability and reversibility in gene expression programmes to maintain cell identity or to enable responses to stimuli; epigenetic regulation is integral to this dynamic control. Post-translational modification of histones by methylation is an important and widespread type of chromatin modification that is known to influence biological processes in the context of development and cellular responses. To evaluate how histone methylation contributes to stable or reversible control, we provide a broad overview of how histone methylation is regulated and leads to biological outcomes. The importance of appropriately maintaining or reprogramming histone methylation is illustrated by its links to disease and ageing and possibly to transmission of traits across generations.

1,711 citations

Journal ArticleDOI
TL;DR: Physiological roles for protein arginine methylation have been established in signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation.

1,525 citations

Journal ArticleDOI
TL;DR: These transcriptional paradigms provide a basic framework for understanding the integration of mitochondrial biogenesis and function with signaling events that dictate cell- and tissue-specific energetic properties.
Abstract: Mitochondria contain their own genetic system and undergo a unique mode of cytoplasmic inheritance. Each organelle has multiple copies of a covalently closed circular DNA genome (mtDNA). The entire...

1,401 citations

Journal ArticleDOI
TL;DR: This review summarizes the understanding of the transcriptional regulatory mechanisms involved in the biogenesis and energy metabolic function of mitochondria in higher organisms.
Abstract: We are witnessing a period of renewed interest in the biology of the mitochondrion. The mitochondrion serves a critical function in the maintenance of cellular energy stores, thermogenesis, and apoptosis. Moreover, alterations in mitochondrial function contribute to several inherited and acquired human diseases and the aging process. This review summarizes our understanding of the transcriptional regulatory mechanisms involved in the biogenesis and energy metabolic function of mitochondria in higher organisms.

1,181 citations

19 Apr 2011
TL;DR: Administration of spermidine markedly extended the lifespan of yeast, flies and worms, and human immune cells and inhibited oxidative stress in ageing mice, and found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.
Abstract: Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells In addition, spermidine administration potently inhibited oxidative stress in ageing mice In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity

974 citations