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Yoshitane H.,University of Tokyo | Honma S.,Hokkaido University | Imamura K.,University of Tokyo | Nakajima H.,Daiichi Sankyo | And 10 more authors.
EMBO Reports | Year: 2012

The posttranslational regulation of mammalian clock proteins has been assigned a time-keeping function, but seems to have more essential roles. Here we show that c-Jun N-terminal kinase (JNK), identified by inhibitor screening of BMAL1 phosphorylation at Ser 520/Thr 527/Ser 592, confers dynamic regulation on the clock. Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. Mice deficient for neuron-specific isoform JNK3 have altered behavioural rhythms, with longer free-running period and compromised phase shifts to light. The locomotor rhythms are insensitive to intensity variance of constant light, deviating from Aschoff's rule. Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light. © 2012 European Molecular Biology Organization. Source


Inoue M.,Kurume University | Yasuda K.,Kurume University | Uemura H.,Nagasaki University | Yasaka N.,Kurume University | And 8 more authors.
Journal of Biochemistry | Year: 2013

Hetero- and homodimerization of 14-3-3 proteins demonstrate distinctive functions in mammals and plants. Trypanosoma brucei 14-3-3I and II (Tb14-3-3I and II) play pivotal roles in motility, cytokinesis and the cell cycle; however, the significance and the mechanism of Tb14-3-3 dimerization are remained to be elucidated. We found that ectopically expressed epitope-tagged Tb14-3-3I and II proteins formed hetero- and homodimers with endogenous Tb14-3-3I and II proteins. However, we also found the ability to form hetero- or homodimers between Tb14-3-3I and II proteins was clearly affected by the sequence and location of the epitope tag used. We found a blue native polyacrylamide gel electrophoresis system followed by western blotting may distinguish monomer from dimer structure, and stable from unstable conformation of Tb14-3-3. Combined with co-immunoprecipitation results, we revealed that Tb14-3-3 proteins mainly existed as heterodimeric form. Furthermore, co-overexpression of Tb14-3-3I and II proteins in T. brucei induced aberrant numbers of organelles in cells, but overexpression of either isoform alone rarely produced such morphology. These results suggest that heterodimers play more significant roles than homodimers not only in the maintenance of steady-state levels of the 14-3-3 proteins but also in the regulation of cytokinesis. © 2013 The Authors 2013. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. Source


Isumi Y.,Daiichi Sankyo | Hirata T.,Daiichi Sankyo | Saitoh H.,Daiichi Sankyo | Miyakawa T.,Daiichi Sankyo | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

We found a novel protein-protein interaction between ubiquitin-specific protease 15 (USP15) and skeletal muscle LIM protein 1 (SLIM1): USP15 and SLIM1 directly bound under cell-free conditions and co-immunoprecipitated from the lysates of the cells, where they were co-expressed; and USP15 deubiquitinated SLIM1, resulting in the increase of protein levels of SLIM1. Because SLIM1 is strongly implicated in the pathogenesis of myopathies and cardiomyopathies, we generated transgenic (TG) mice with cardiac-specific overexpression of human USP15. Heart weight to body weight ratios and mRNA levels of fetal gene markers in the heart were significantly higher in USP15-TG mice than in wild-type (WT) mice. Also, protein levels of endogenous murine SLIM1 in the heart were significantly higher in USP15-TG mice than in WT mice. Furthermore, the protein of alternatively spliced isoform of SLIM1 was only detected in the heart of USP15-TG mice, and mRNA levels of this isoform were higher as compared to WT mice. These results indicate that USP15 is involved in the regulation of hypertrophic responses in cardiac muscle through transcriptional and post-translational modulation of SLIM1. © 2011 Elsevier Inc. Source


Trademark
Celestar Lexico science Inc. | Date: 2003-03-04

Computer programs for use in analyzing and visualizing nucleic acid, protein, and phage information and expression; for use in database management, integration and manipulation; for use in characterization of nucleic acid and protein information; for use in analyzing chemical structure and activity information; for use in acquisition and interrogation of clinical, pathological, diagnostic, genetic, genomic and biochemical data; for use in clinical trial design and management; for use in text and pattern recognition; for storage, retrieval and analysis of life sciences literature; for use in managing robot function; for use in processing toxicological and pharmacological information; for laboratory instrument control; for use in control of sample input to mass spectrometers; for use in spectral analysis; prerecorded CD-ROMs featuring databases containing life sciences information; pre-configured microprocessors for analysis and storage of life sciences information; computer programs for use in the management, storage, retrieval, and analysis for data in the discovery and development of diagnostic, prognostic, and therapeutic medical products; for use in identifying and characterizing proteins; for use in controlling mass spectrometers; for use in spectral analysis; for use in controlling affinity capture optical biosensors; for use in analyzing and characterizing plasmon resonance; for use in controlling liquid chromatography instruments; for use in analyzing chromatograms; for use in controlling microfluidics; for use in controlling single-dimension and multi-dimensional electrophoresis and visualizing and analyzing electrophoretic results; for use in protein analysis and spectral processing; for use in analyzing, managing, and visualizing nucleic acid and amino acid sequences. Medical and diagnostic services, namely, diagnosing, preventing, and predicting disease, identifying hereditary risk factors, diagnostic testing, prognostic testing, gene and protein testing, identifying physiological characteristics, establishing individual preventative programs, establishing disease treatment based on gene and protein expression and/or activity, evaluating clinical trial progress, drug monitoring and computer tracking of a patients health progress; research services, namely, research, development, validation, testing, data analysis and product development services in the biomedical, genomic, pharmacogenomic, diagnostic, clinical trial design, and biotechnology fields; research consulting services, namely, research, development, validation, testing, data analysis, and product development services for others in the biomedical, genomic, pharmaceutical, pharmacogenomic, diagnostic, clinical trial design, and biotechnology fields; computer services, namely, providing databases featuring life sciences information via global, national, and local computer networks in the fields of pharmacogenomics, diagnostics, clinical trial design and biotechnology; computer consulting services, namely, providing databases featuring life sciences information to others via global, national, and local computer networks in the fields of pharmacogenomics, diagnostics, clinical trial design and biotechnology.


Trademark
Celestar Lexico science Inc. | Date: 2003-03-04

Computer programs for use in analyzing and visualizing nucleic acid, protein, and phage information and expression; for use in database management, integration and manipulation; for use in characterization of nucleic acid and protein information; for use in analyzing chemical structure and activity information; for use in acquisition and interrogation of clinical, pathological, diagnostic, genetic, genomic and biochemical data; for use in clinical trial design and management; for use in text and pattern recognition; for storage, retrieval and analysis of life sciences literature; for use in managing robot function; for use in processing toxicological and pharmacological information; for laboratory instrument control; for use in control of sample input to mass spectrometers; for use in spectral analysis; prerecorded CD-ROMs featuring databases containing life sciences information; pre-configured microprocessors for analysis and storage of life sciences information; computer programs for use in the management, storage, retrieval, and analysis for data in the discovery and development of diagnostic, prognostic, and therapeutic medical products; for use in identifying and characterizing proteins; for use in controlling mass spectrometers; for use in spectral analysis; for use in controlling affinity capture optical biosensors; for use in analyzing and characterizing plasmon resonance; for use in controlling liquid chromatography instruments; for use in analyzing chromatograms; for use in controlling microfluidics; for use in controlling single-dimension and multi-dimensional electrophoresis and visualizing and analyzing electrophoretic results; for use in protein analysis and spectral processing; for use in analyzing, managing, and visualizing nucleic acid and amino acid sequences. Medical and diagnostic services, namely, diagnosing, preventing, and predicting disease, identifying hereditary risk factors, diagnostic testing, prognostic testing, gene and protein testing, identifying physiological characteristics, establishing individual preventative programs, establishing disease treatment based on gene and protein expression and/or activity, evaluating clinical trial progress, drug monitoring and computer tracking of a patients health progress; research services, namely, research, development, validation, testing, data analysis and product development services in the biomedical, genomic, pharmacogenomic, diagnostic, clinical trial design, and biotechnology fields; research consulting services, namely, research, development, validation, testing, data analysis, and product development services for others in the biomedical, genomic, pharmaceutical, pharmacogenomic, diagnostic, clinical trial design, and biotechnology fields; computer services, namely, providing databases featuring life sciences information via global, national, and local computer networks in the fields of pharmacogenomics, diagnostics, clinical trial design and biotechnology; computer consulting services, namely, providing databases featuring life sciences information to others via global, national, and local computer networks in the fields of pharmacogenomics, diagnostics, clinical trial design and biotechnology.

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