{alpha}-Klotho mice demonstrate increased expression of the non-sulfated N-glycan form of the HNK-1 glyco-epitope in kidney tissue
The α-Klotho mouse is an animal model that prematurely exhibits phenotypes resembling human aging owing to mutation of the α-Klotho gene. Although α-Klotho mice appear normal at birth, they begin showing multiple age-associated disorders after 3–4 weeks. Meanwhile, overexpression of α-Klotho extends lifespan. Therefore, α-Klotho may be involved in the aging process. The α-Klotho protein has homology to β-glucosidase and is proposed to have glycosidase activity. However, it is unclear whether glycan alterations are present in α-Klotho mice. Here we found increased levels ...
Source: Journal of Biochemistry - July 28, 2014 Category: Biochemistry Authors: Akasaka-Manya, K., Manya, H., Kizuka, Y., Oka, S., Endo, T. Tags: Regular Papers Source Type: research
Crystal structure of truncated haemoglobin from an extremely thermophilic and acidophilic bacterium
A truncated haemoglobin (tHb) has been identified in an acidophilic and thermophilic methanotroph Methylacidiphilium infernorum. Hell’s Gate Globin IV (HGbIV) and its related tHbs differ from all other bacterial tHbs due to their distinctively large sequence and polar distal haem pocket residues. Here we report the crystal structure of HGbIV determined at 1.96 Å resolution. The HGbIV structure has the distinctive 2/2 α-helical structure with extensions at both termini. It has a large distal site cavity in the haem pocket surrounded by four polar residues: His70(B9), His71(B10), Ser97(E11) and Trp137(G8). ...
Source: Journal of Biochemistry - July 28, 2014 Category: Biochemistry Authors: Jamil, F., Teh, A.-H., Schadich, E., Saito, J. A., Najimudin, N., Alam, M. Tags: Regular Papers Source Type: research
Most hydrogen peroxide-induced histone H2AX phosphorylation is mediated by ATR and is not dependent on DNA double-strand breaks
The nuclear foci of phosphorylated histone H2AX (H2AX) are frequently used as a marker for DNA double-strand breaks (DSBs) following ionizing radiation (IR). However, recent studies reported that H2AX foci do not necessarily correlate with DSBs under other conditions. We showed that H2AX foci induced by oxidative stress in hydrogen peroxide (H2O2)-treated cells displayed several different features from those induced by IR. The magnitude of H2AX induction was heterogeneous among H2O2-treated cells. Some cells expressed small discrete H2AX foci, whereas others expressed a gross H2AX signal that was distributed throughout the...
Source: Journal of Biochemistry - July 28, 2014 Category: Biochemistry Authors: Katsube, T., Mori, M., Tsuji, H., Shiomi, T., Wang, B., Liu, Q., Nenoi, M., Onoda, M. Tags: Regular Papers Source Type: research
Pleiotropic roles of mTOR complexes in haemato-lymphopoiesis and leukemogenesis
Mammalian/mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that responds to environmental determinants such as growth factor concentration, nutrient availability, energy sufficiency and stress. mTOR forms two different complexes, called mTOR complex 1 (mTORC1) and mTORC2, and these complexes have distinct substrate molecules that function in the regulation of protein translation and cellular metabolism. Although mTOR was originally discovered as a target protein of rapamycin, a natural macrolide immunosuppressant, rapamycin mainly inhibits the kinase activity of mTORC1, whereas mTORC2 is...
Source: Journal of Biochemistry - July 28, 2014 Category: Biochemistry Authors: Hoshii, T., Matsuda, S., Hirao, A. Tags: JB Reviews Source Type: research
DNA methylation accumulation and its predetermination of future cancer phenotypes
Aberant DNA methylation is a common epigenomic alteration in carcinogenesis. Comprehensive analyses of DNA methylation have stratified gastrointestinal cancer into several subgroups according to specific DNA methylation accumulation. In gastric cancer, Helicobacter pylori infection is a cause of methylation accumulation in apparently normal mucosa. Epstein–Barr virus infection is another methylation inducer that causes more genome-wide methylation, resulting in the formation of unique epigenotype with extensive methylation. In colorectal carcinogenesis, accumulation of high levels of methylation in combination with B...
Source: Journal of Biochemistry - July 28, 2014 Category: Biochemistry Authors: Kaneda, A., Matsusaka, K., Sakai, E., Funata, S. Tags: JB Reviews Source Type: research
Cellular localization of CoPK12, a Ca2+/calmodulin-dependent protein kinase in mushroom Coprinopsis cinerea, is regulated by N-myristoylation
Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) have been extensively studied in mammals, whereas fungus CaMKs still remain largely uncharacterized. We previously obtained CaMK homolog in Coprinopsis cinerea, designated CoPK12, and revealed its unique catalytic properties in comparison with the mammalian CaMKs. To further clarify the regulatory mechanisms of CoPK12, we investigated post-translational modification and subcellular localization of CoPK12 in this study. In C. cinerea, full-length CoPK12 (65 kDa) was fractionated in the membrane fraction, while the catalytically active fragment (46 kDa) of CoP...
Source: Journal of Biochemistry - June 26, 2014 Category: Biochemistry Authors: Kaneko, K., Tabuchi, M., Sueyoshi, N., Ishida, A., Utsumi, T., Kameshita, I. Tags: Regular Papers Source Type: research
Constitutive expression of a COOH-terminal leucine mutant of lysosome-associated membrane protein-1 causes its exclusive localization in low density intracellular vesicles
In this study, we generated two human hepatoma cell lines (HepG2 cell lines) that stably express WT-LAMP-1 and I382L, and compared their intracellular distributions. The subcellular fractionation study using Percoll density gradient centrifugation revealed that WT-LAMP-1 had preferential localization in the high density secondary lysosomes where endogenous human LAMP-1 was enriched. In contrast, a major portion of I382L was located in a low density fraction. The low density fraction also contained approximately 80% of endogenous human LAMP-1 and significant amounts of endogenous β-glucuronidase and LAMP-2, which proba...
Source: Journal of Biochemistry - June 26, 2014 Category: Biochemistry Authors: Akasaki, K., Shiotsu, K., Michihara, A., Ide, N., Wada, I. Tags: Regular Papers Source Type: research
Ryk is essential for Wnt-5a-dependent invasiveness in human glioma
Glioblastoma is characterized by marked invasiveness, but little is known about the mechanism of invasion in glioblastoma cells. Wnts are secreted ligands that regulate cell proliferation, differentiation, motility and fate at various developmental stages. In adults, misregulation of the Wnt pathway is associated with several diseases. Recently, we reported that Wnt-5a was overexpressed and correlated with cell motility and infiltrative activity through the regulation of matrix metalloproteinase (MMP)-2 in glioma-derived cells. Although several receptors for Wnt-5a were identified, the receptors of Wnt-5a that mediate cell...
Source: Journal of Biochemistry - June 26, 2014 Category: Biochemistry Authors: Habu, M., Koyama, H., Kishida, M., Kamino, M., Iijima, M., Fuchigami, T., Tokimura, H., Ueda, M., Tokudome, M., Koriyama, C., Hirano, H., Arita, K., Kishida, S. Tags: Regular Papers Source Type: research
A candidate enhancer element responsible for high-level expression of the aggrecan gene in chondrocytes
Aggrecan is the most abundant proteoglycan in cartilage. It contains a lot of negatively charged glycosaminoglycan chains along the core protein, providing a large osmotic swelling pressure within the cartilage. Therefore, the biomechanical properties of cartilage, such as its compressive load-bearing capacity, are highly dependent on the presence of abundant aggrecan in the cartilage matrix. To elucidate the transcriptional mechanism that leads to abundant expression of aggrecan by chondrocytes, we screened for enhancer elements in 130 kb of the aggrecan gene, Agc1, using a reporter assay system that we previously develop...
Source: Journal of Biochemistry - June 26, 2014 Category: Biochemistry Authors: Ikeda, Y., Ito, K., Izumi, Y., Shinomura, T. Tags: Regular Papers Source Type: research
Biochemical and structural properties of heterochromatin protein 1: understanding its role in chromatin assembly
Heterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that binds lysine 9-methylated histone H3 (H3K9me), a hallmark of heterochromatin, and plays a crucial role in forming higher-order chromatin structures. HP1 has an N-terminal chromodomain and a C-terminal chromo shadow domain, linked by an unstructured hinge region. Although biochemical and structural studies have revealed each domain’s properties, little is known about the mechanisms by which these domains cooperate to carry out HP1’s function in forming higher-order chromatin structures. In this review, we summarize HP1’...
Source: Journal of Biochemistry - June 26, 2014 Category: Biochemistry Authors: Nishibuchi, G., Nakayama, J.-i. Tags: JB Reviews Source Type: research
Roles of VEGF-A signalling in development, regeneration, and tumours
Angiogenesis, the formation of new networks of blood vessels, has essential roles in embryonic development, organ homeostasis and disease progression. Several signalling molecules, such as vascular endothelial growth factors (VEGFs), fibroblast growth factors (FGFs), transforming growth factor (TGF)-β and angiopoietin-1 and 2, are known to be key regulators of blood vessel development and network patterning. Among these, the roles of VEGF-A and its receptors in vessel morphogenesis are understood best. VEGF-A signalling plays a crucial role in embryonic development through the regulation of angiogenesis. VEGF-A regula...
Source: Journal of Biochemistry - June 26, 2014 Category: Biochemistry Authors: Matsumoto, K., Ema, M. Tags: JB Reviews Source Type: research
Proposing a new RNA quadruplex structure: j-motif, with possible links to neural development
An RNA-binding protein, hnRNP K, has been studied extensively because of its involvement in neural development through the post-transcriptional regulation of its downstream target genes; however, its binding mode remains unclear. According to structural features of the binding sites, we have presumed the existence of possible unique structures ‘j-motifs’ that are similar to known i-motifs, the difference being that the initial cluster comprises successive U nucleic acids instead of C. It was suspected that the motifs could be recognized by hnRNP K to regulate the translation levels of target proteins, however, ...
Source: Journal of Biochemistry - May 27, 2014 Category: Biochemistry Authors: Nakamura, S., Igarashi, M., Kinoshita, M., Okano, H. J., Okano, H. Tags: Regular Papers Source Type: research
Trimming of glucosylated N-glycans by human ER {alpha}1,2-mannosidase I
In this study, we revealed that this enzyme also accepts N-linked sugar chains with glucose moieties as substrates with nearly identical reactivity. The ability of hERManI to remove mannose residues from GlcMan9GlcNAc2 in model glycoproteins, such as Aspergillus oryzae β-galactosidase and chicken immunoglobulin Y (IgY), was markedly augmented when glycoproteins were denatured. The properties of hERManI enable rapid selection of ERAD substrates in the ER and may help maintain homeostasis of sugar metabolism in living organisms. (Source: Journal of Biochemistry)
Source: Journal of Biochemistry - May 27, 2014 Category: Biochemistry Authors: Aikawa, J.-i., Takeda, Y., Matsuo, I., Ito, Y. Tags: Regular Papers Source Type: research
Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel
Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by...
Source: Journal of Biochemistry - May 27, 2014 Category: Biochemistry Authors: Kachooei, E., Moosavi-Movahedi, A. A., Khodagholi, F., Mozaffarian, F., Sadeghi, P., Hadi-Alijanvand, H., Ghasemi, A., Saboury, A. A., Farhadi, M., Sheibani, N. Tags: Regular Papers Source Type: research
Phosphorylation of Grb14 BPS domain by GSK-3 correlates with complex forming of Grb14 and insulin receptor
Growth factor receptor-bound protein 14 (Grb14) interacts with insulin receptor (IR) through the between PH and SH2 (BPS) domain. Grb14–IR complex formation is initiated by insulin stimulation, and the binding event results in the inhibition of insulin signalling. Thus, Grb14 is regarded as an endogenous suppressor of insulin signal transduction; however, there are no studies describing the mechanism whereby Grb14–IR complex formation is suppressed in the absence of insulin stimulation. In the present study, multiple phosphorylation motifs for glycogen synthase kinase 3 (GSK-3) were identified within the Grb14 ...
Source: Journal of Biochemistry - May 27, 2014 Category: Biochemistry Authors: Taira, J., Higashimoto, Y. Tags: Regular Papers Source Type: research
