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  • 1
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    Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1 (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-01-29
    Description: Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha-/- fibroblasts were impaired in JNK activation by ER stress. The cytoplasmic part of IRE1 bound TRAF2, an adaptor protein that couples plasma membrane receptors to JNK activation. Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Urano, F -- Wang, X -- Bertolotti, A -- Zhang, Y -- Chung, P -- Harding, H P -- Ron, D -- DK47119/DK/NIDDK NIH HHS/ -- ES08681/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):664-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10650002" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Endoplasmic Reticulum/*metabolism ; Endoribonucleases/genetics/*metabolism ; Enzyme Activation ; Gene Targeting ; Humans ; JNK Mitogen-Activated Protein Kinases ; *Membrane Proteins ; Mitogen-Activated Protein Kinases/*metabolism ; Multienzyme Complexes/genetics/*metabolism ; Protein Kinases/genetics/*metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Proteins/chemistry/genetics/*metabolism ; Rats ; Recombinant Fusion Proteins/metabolism ; TNF Receptor-Associated Factor 2 ; Thapsigargin/pharmacology ; Two-Hybrid System Techniques ; eIF-2 Kinase/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-02-05
    Description: A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins. A protein was engineered so that it accumulated as aggregates in the endoplasmic reticulum. Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation. Rapid and transient secretion of growth hormone and insulin was achieved in vitro and in vivo. A regulated pulse of insulin secretion resulted in a transient correction of serum glucose concentrations in a mouse model of hyperglycemia. This approach may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rivera, V M -- Wang, X -- Wardwell, S -- Courage, N L -- Volchuk, A -- Keenan, T -- Holt, D A -- Gilman, M -- Orci, L -- Cerasoli, F Jr -- Rothman, J E -- Clackson, T -- New York, N.Y. -- Science. 2000 Feb 4;287(5454):826-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ARIAD Gene Therapeutics, 26 Landsdowne Street, Cambridge, MA 02139, USA. vrivera@ariad.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10657290" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/metabolism ; Cell Line ; Diabetes Mellitus, Experimental/drug therapy/metabolism ; Drug Delivery Systems ; Endoplasmic Reticulum/*metabolism/secretion ; Furin ; Genetic Therapy ; Golgi Apparatus/metabolism ; Human Growth Hormone/chemistry/metabolism/secretion ; Humans ; Immunophilins/chemistry/genetics/metabolism ; Insulin/secretion ; Kinetics ; Ligands ; Mice ; Proinsulin/chemistry/metabolism ; Protein Engineering ; Recombinant Fusion Proteins/*chemistry/*metabolism/secretion ; Subtilisins/metabolism ; Tacrolimus Binding Proteins ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-11-26
    Description: Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to apoptotic signals. However, the mechanisms underlying this process have not been resolved. We report that inactivation of the Caenorhabditis elegans AIF homolog wah-1 by RNA interference delayed the normal progression of apoptosis and caused a defect in apoptotic DNA degradation. WAH-1 localized in C. elegans mitochondria and was released into the cytosol and nucleus by the BH3-domain protein EGL-1 in a caspase (CED-3)-dependent manner. In addition, WAH-1 associated and cooperated with the mitochondrial endonuclease CPS-6/endonuclease G (EndoG) to promote DNA degradation and apoptosis. Thus, AIF and EndoG define a single, mitochondria-initiated apoptotic DNA degradation pathway that is conserved between C. elegans and mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiaochen -- Yang, Chonglin -- Chai, Jijie -- Shi, Yigong -- Xue, Ding -- New York, N.Y. -- Science. 2002 Nov 22;298(5598):1587-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12446902" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Apoptosis ; Apoptosis Inducing Factor ; Caenorhabditis elegans/cytology/embryology/genetics/*physiology ; Caenorhabditis elegans Proteins/chemistry/genetics/*physiology ; Caspases/metabolism ; Cell Nucleus/metabolism ; Cell Survival ; Cloning, Molecular ; Cytosol/metabolism ; *DNA Fragmentation ; DNA, Helminth/*metabolism ; Endodeoxyribonucleases/metabolism ; Flavoproteins/physiology ; Humans ; In Situ Nick-End Labeling ; Membrane Proteins/physiology ; Mitochondria/metabolism ; Mitochondrial Proteins/chemistry/genetics/*physiology ; Molecular Sequence Data ; Mutation ; Phenotype ; RNA Interference ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/metabolism ; Sequence Alignment
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-05-30
    Description: With the recent recognition of non-coding RNAs (ncRNAs) flanking many genes, a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms. Here we show that an RNA-binding protein, TLS (for translocated in liposarcoma), serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CREB-binding protein (CBP) and p300 histone acetyltransferase activities on a repressed gene target, cyclin D1 (CCND1) in human cell lines. Recruitment of TLS to the CCND1 promoter to cause gene-specific repression is directed by single-stranded, low-copy-number ncRNA transcripts tethered to the 5' regulatory regions of CCND1 that are induced in response to DNA damage signals. Our data suggest that signal-induced ncRNAs localized to regulatory regions of transcription units can act cooperatively as selective ligands, recruiting and modulating the activities of distinct classes of RNA-binding co-regulators in response to specific signals, providing an unexpected ncRNA/RNA-binding protein-based strategy to integrate transcriptional programmes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823488/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823488/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiangting -- Arai, Shigeki -- Song, Xiaoyuan -- Reichart, Donna -- Du, Kun -- Pascual, Gabriel -- Tempst, Paul -- Rosenfeld, Michael G -- Glass, Christopher K -- Kurokawa, Riki -- CA097134/CA/NCI NIH HHS/ -- CA52599/CA/NCI NIH HHS/ -- DK074868/DK/NIDDK NIH HHS/ -- DK39949/DK/NIDDK NIH HHS/ -- HL59694/HL/NHLBI NIH HHS/ -- NS34934/NS/NINDS NIH HHS/ -- P30 CA08748/CA/NCI NIH HHS/ -- R01 CA052599/CA/NCI NIH HHS/ -- R01 CA052599-19/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 HL059694/HL/NHLBI NIH HHS/ -- R01 HL059694-10/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-20A1/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- R37 DK039949-26/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Jul 3;454(7200):126-30. doi: 10.1038/nature06992. Epub 2008 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509338" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; CREB-Binding Protein/antagonists & inhibitors/metabolism ; Cell Line ; Consensus Sequence ; Cyclin D1/genetics ; DNA Damage ; *Down-Regulation ; HeLa Cells ; Histone Acetyltransferases/antagonists & inhibitors/metabolism ; Humans ; Oligonucleotides/genetics ; Promoter Regions, Genetic/genetics ; RNA, Untranslated/genetics/*metabolism ; RNA-Binding Protein FUS/genetics/*metabolism ; *Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    HITS-CLIP yields genome-wide insights into brain alternative RNA processing (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-11-04
    Description: Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597294/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597294/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Licatalosi, Donny D -- Mele, Aldo -- Fak, John J -- Ule, Jernej -- Kayikci, Melis -- Chi, Sung Wook -- Clark, Tyson A -- Schweitzer, Anthony C -- Blume, John E -- Wang, Xuning -- Darnell, Jennifer C -- Darnell, Robert B -- MC_U105185858/Medical Research Council/United Kingdom -- R01 NS034389/NS/NINDS NIH HHS/ -- R01 NS034389-09/NS/NINDS NIH HHS/ -- R01 NS034389-10/NS/NINDS NIH HHS/ -- R01 NS034389-11/NS/NINDS NIH HHS/ -- R01 NS034389-12/NS/NINDS NIH HHS/ -- R01 NS034389-13A1/NS/NINDS NIH HHS/ -- R01 NS040955/NS/NINDS NIH HHS/ -- R01 NS040955-05/NS/NINDS NIH HHS/ -- R01 NS34389/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Nov 27;456(7221):464-9. doi: 10.1038/nature07488. Epub 2008 Nov 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18978773" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/*genetics ; Animals ; Antigens, Neoplasm/genetics/*metabolism ; Cell Line ; Cross-Linking Reagents/chemistry/metabolism ; Exons/genetics ; Genome/*genetics ; Genomics ; Humans ; Immunoprecipitation ; Mice ; Neocortex/*cytology ; Neurons/*metabolism ; Organ Specificity ; Polyadenylation/genetics ; RNA, Messenger/genetics/*metabolism ; RNA-Binding Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Structural insight into the autoinhibition mechanism of AMP-activated protein kinase (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-05-29
    Description: The AMP-activated protein kinase (AMPK) is characterized by its ability to bind to AMP, which enables it to adjust enzymatic activity by sensing the cellular energy status and maintain the balance between ATP production and consumption in eukaryotic cells. It also has important roles in the regulation of cell growth and proliferation, and in the establishment and maintenance of cell polarity. These important functions have rendered AMPK an important drug target for obesity, type 2 diabetes and cancer treatments. However, the regulatory mechanism of AMPK activity by AMP binding remains unsolved. Here we report the crystal structures of an unphosphorylated fragment of the AMPK alpha-subunit (KD-AID) from Schizosaccharomyces pombe that contains both the catalytic kinase domain and an autoinhibitory domain (AID), and of a phosphorylated kinase domain from Saccharomyces cerevisiae (Snf1-pKD). The AID binds, from the 'backside', to the hinge region of its kinase domain, forming contacts with both amino-terminal and carboxy-terminal lobes. Structural analyses indicate that AID binding might constrain the mobility of helix alphaC, hence resulting in an autoinhibited KD-AID with much lower kinase activity than that of the kinase domain alone. AMP activates AMPK both allosterically and by inhibiting dephosphorylation. Further in vitro kinetic studies demonstrate that disruption of the KD-AID interface reverses the autoinhibition and these AMPK heterotrimeric mutants no longer respond to the change in AMP concentration. The structural and biochemical data have shown the primary mechanism of AMPK autoinhibition and suggest a conformational switch model for AMPK activation by AMP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Jiao, Zhi-Hao -- Zheng, Li-Sha -- Zhang, Yuan-Yuan -- Xie, Shu-Tao -- Wang, Zhi-Xin -- Wu, Jia-Wei -- England -- Nature. 2009 Jun 25;459(7250):1146-9. doi: 10.1038/nature08075. Epub 2009 May 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MOE Key Laboratory of Bioinformatics, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19474788" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*chemistry/*metabolism ; Adenosine Monophosphate/metabolism ; Amino Acid Sequence ; Animals ; *Models, Molecular ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein Structure, Tertiary ; Rats ; Saccharomyces cerevisiae/*enzymology ; Schizosaccharomyces/*enzymology ; Sequence Alignment
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-02-24
    Description: Life and death fate decisions allow cells to avoid massive apoptotic death in response to genotoxic stress. Although the regulatory mechanisms and signalling pathways controlling DNA repair and apoptosis are well characterized, the precise molecular strategies that determine the ultimate choice of DNA repair and survival or apoptotic cell death remain incompletely understood. Here we report that a protein tyrosine phosphatase, EYA, is involved in promoting efficient DNA repair rather than apoptosis in response to genotoxic stress in mammalian embryonic kidney cells by executing a damage-signal-dependent dephosphorylation of an H2AX carboxy-terminal tyrosine phosphate (Y142). This post-translational modification determines the relative recruitment of either DNA repair or pro-apoptotic factors to the tail of serine phosphorylated histone H2AX (gamma-H2AX) and allows it to function as an active determinant of repair/survival versus apoptotic responses to DNA damage, revealing an additional phosphorylation-dependent mechanism that modulates survival/apoptotic decisions during mammalian organogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692521/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, Peter J -- Ju, Bong Gun -- Telese, Francesca -- Wang, Xiangting -- Glass, Christopher K -- Rosenfeld, Michael G -- R01 CA097134/CA/NCI NIH HHS/ -- R01 CA097134-06A1/CA/NCI NIH HHS/ -- R01 CA097134-07/CA/NCI NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 DK039949-17S1/DK/NIDDK NIH HHS/ -- R01 DK039949-18/DK/NIDDK NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 HL065445-08/HL/NHLBI NIH HHS/ -- R01 HL065445-09/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-18/NS/NINDS NIH HHS/ -- R01 NS034934-19/NS/NINDS NIH HHS/ -- R01 NS034934-20A1/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Apr 2;458(7238):591-6. doi: 10.1038/nature07849. Epub 2009 Feb 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute School of Medicine, University of California, San Diego, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19234442" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/metabolism ; Cell Line ; Cell Survival ; DNA Damage ; DNA Repair ; DNA-Binding Proteins/deficiency/genetics/metabolism ; Histones/deficiency/genetics/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/deficiency/genetics/metabolism ; Mice ; Nuclear Proteins/deficiency/genetics/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Binding ; Protein Tyrosine Phosphatases/deficiency/genetics/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Substrate Specificity ; Tumor Suppressor Proteins/metabolism ; Tyrosine/*metabolism
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-01-06
    Description: Insulin resistance, a hallmark of type 2 diabetes, is a defect of insulin in stimulating insulin receptor signalling, which has become one of the most serious public health threats. Upon stimulation by insulin, insulin receptor recruits and phosphorylates insulin receptor substrate proteins, leading to activation of the phosphatidylinositol-3-OH kinase (PI(3)K)-Akt pathway. Activated Akt phosphorylates downstream kinases and transcription factors, thus mediating most of the metabolic actions of insulin. Beta-arrestins mediate biological functions of G-protein-coupled receptors by linking activated receptors with distinct sets of accessory and effecter proteins, thereby determining the specificity, efficiency and capacity of signals. Here we show that in diabetic mouse models, beta-arrestin-2 is severely downregulated. Knockdown of beta-arrestin-2 exacerbates insulin resistance, whereas administration of beta-arrestin-2 restores insulin sensitivity in mice. Further investigation reveals that insulin stimulates the formation of a new beta-arrestin-2 signal complex, in which beta-arrestin-2 scaffolds Akt and Src to insulin receptor. Loss or dysfunction of beta-arrestin-2 results in deficiency of this signal complex and disturbance of insulin signalling in vivo, thereby contributing to the development of insulin resistance and progression of type 2 diabetes. Our findings provide new insight into the molecular pathogenesis of insulin resistance, and implicate new preventive and therapeutic strategies against insulin resistance and type 2 diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luan, Bing -- Zhao, Jian -- Wu, Haiya -- Duan, Baoyu -- Shu, Guangwen -- Wang, Xiaoying -- Li, Dangsheng -- Jia, Weiping -- Kang, Jiuhong -- Pei, Gang -- England -- Nature. 2009 Feb 26;457(7233):1146-9. doi: 10.1038/nature07617.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, and Graduate School of the Chinese Academy of Sciences.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19122674" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*deficiency/genetics/pharmacology ; Cell Line ; Cell Line, Tumor ; Diabetes Mellitus, Type 2/metabolism ; Disease Models, Animal ; Down-Regulation ; Gene Knockdown Techniques ; Humans ; Insulin/pharmacology ; Insulin Resistance/genetics/*physiology ; Mice ; Mice, Knockout ; Mutation/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; Receptor, Insulin/metabolism ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Calcium flickers steer cell migration (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-01-02
    Description: Directional movement is a property common to all cell types during development and is critical to tissue remodelling and regeneration after damage. In migrating cells, calcium has a multifunctional role in directional sensing, cytoskeleton redistribution, traction force generation, and relocation of focal adhesions. Here we visualize high-calcium microdomains ('calcium flickers') and their patterned activation in migrating human embryonic lung fibroblasts. Calcium flicker activity is dually coupled to membrane tension (by means of TRPM7, a stretch-activated Ca(2+)-permeant channel of the transient receptor potential superfamily) and chemoattractant signal transduction (by means of type 2 inositol-1,4,5-trisphosphate receptors). Interestingly, calcium flickers are most active at the leading lamella of migrating cells, displaying a 4:1 front-to-rear polarization opposite to the global calcium gradient. When exposed to a platelet-derived growth factor gradient perpendicular to cell movement, asymmetric calcium flicker activity develops across the lamella and promotes the turning of migrating fibroblasts. These findings show how the exquisite spatiotemporal organization of calcium microdomains can orchestrate complex cellular processes such as cell migration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505761/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505761/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wei, Chaoliang -- Wang, Xianhua -- Chen, Min -- Ouyang, Kunfu -- Song, Long-Sheng -- Cheng, Heping -- HL090905/HL/NHLBI NIH HHS/ -- R01 HL090905/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Feb 12;457(7231):901-5. doi: 10.1038/nature07577. Epub 2008 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871, China. chaoliang.wei@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19118385" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/*metabolism ; Calcium-Transporting ATPases/antagonists & inhibitors ; Cell Line ; Cell Polarity/physiology ; Chemotaxis/drug effects/*physiology ; Endoplasmic Reticulum/drug effects/metabolism ; Enzyme Inhibitors/pharmacology ; Fibroblasts/cytology/physiology ; Gene Expression Regulation, Developmental ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Protein-Serine-Threonine Kinases ; TRPM Cation Channels/metabolism ; Thapsigargin/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-29
    Description: The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogen and nutrient signals to control cell proliferation and cell size. Hence, mTORC1 is implicated in a large number of human diseases--including diabetes, obesity, heart disease, and cancer--that are characterized by aberrant cell growth and proliferation. Although eukaryotic translation initiation factor 4E-binding proteins (4E-BPs) are critical mediators of mTORC1 function, their precise contribution to mTORC1 signaling and the mechanisms by which they mediate mTORC1 function have remained unclear. We inhibited the mTORC1 pathway in cells lacking 4E-BPs and analyzed the effects on cell size, cell proliferation, and cell cycle progression. Although the 4E-BPs had no effect on cell size, they inhibited cell proliferation by selectively inhibiting the translation of messenger RNAs that encode proliferation-promoting proteins and proteins involved in cell cycle progression. Thus, control of cell size and cell cycle progression appear to be independent in mammalian cells, whereas in lower eukaryotes, 4E-BPs influence both cell growth and proliferation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893390/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893390/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dowling, Ryan J O -- Topisirovic, Ivan -- Alain, Tommy -- Bidinosti, Michael -- Fonseca, Bruno D -- Petroulakis, Emmanuel -- Wang, Xiaoshan -- Larsson, Ola -- Selvaraj, Anand -- Liu, Yi -- Kozma, Sara C -- Thomas, George -- Sonenberg, Nahum -- P50 NS057531/NS/NINDS NIH HHS/ -- P50 NS057531-01A2/NS/NINDS NIH HHS/ -- R01 DK078019/DK/NIDDK NIH HHS/ -- R01 DK73802/DK/NIDDK NIH HHS/ -- U01 CA84292-06/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 May 28;328(5982):1172-6. doi: 10.1126/science.1187532.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20508131" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/genetics/*metabolism ; Cell Cycle ; *Cell Enlargement ; Cell Line ; *Cell Proliferation ; Cell Size ; Cell Survival ; Eukaryotic Initiation Factors/genetics/*metabolism ; Humans ; Mice ; Mice, Knockout ; Multiprotein Complexes ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Protein Biosynthesis ; Proteins ; RNA, Messenger/genetics/metabolism ; Ribosomal Protein S6 Kinases/metabolism ; Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases ; Transcription Factors/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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