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  • 1
    Publication Date: 2014-12-17
    Description: We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not sufficient for the inhibition of its DNA-binding activity during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro motif of Sp1 to modulate the interaction between phospho-Sp1 and CDK1, thereby facilitating CDK1-mediated phosphorylation of Sp1 at Ser720, Thr723 and Thr737 during mitosis. Loss of the C-terminal end of Sp1 (amino acids 741-785) significantly increased Sp1 phosphorylation, implying that the C-terminus inhibits CDK1-mediated Sp1 phosphorylation. Binding analysis of Sp1 peptides to Pin1 by isothermal titration calorimetry indicated that Pin1 interacts with Thr739(p)-Sp1 peptide but not with Thr739-Sp1 peptide. X-ray crystallography data showed that the Thr739(p)-Sp1 peptide occupies the active site of Pin1. Increased Sp1 phosphorylation by CDK1 during mitosis not only stabilized Sp1 levels by decreasing interaction with ubiquitin E3-ligase RNF4 but also caused Sp1 to move out of the chromosomes completely by decreasing its DNA-binding activity, thereby facilitating cell cycle progression. Thus, Pin1-mediated conformational changes in the C-terminal region of Sp1 are critical for increased CDK1-mediated Sp1 phosphorylation to facilitate cell cycle progression during mitosis.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-26
    Description: Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation. WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains. Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, P J -- Zhou, X Z -- Shen, M -- Lu, K P -- R01GM56230/GM/NIGMS NIH HHS/ -- R01GM58556/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1325-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10037602" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Calcium-Binding Proteins/chemistry/*metabolism ; Cell Cycle Proteins/metabolism ; Endosomal Sorting Complexes Required for Transport ; HeLa Cells ; Humans ; *Ligases ; Peptidylprolyl Isomerase/chemistry/genetics/*metabolism ; Phosphopeptides/metabolism ; Phosphoproteins/*metabolism ; Phosphorylation ; Phosphoserine/*metabolism ; Phosphothreonine/*metabolism ; Point Mutation ; Signal Transduction ; *Ubiquitin-Protein Ligases ; *cdc25 Phosphatases
    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
    Publication Date: 2008-05-24
    Description: Nanoscale or colloidal particles are important in many realms of science and technology. They can dramatically change the properties of materials, imparting solid-like behaviour to a wide variety of complex fluids. This behaviour arises when particles aggregate to form mesoscopic clusters and networks. The essential component leading to aggregation is an interparticle attraction, which can be generated by many physical and chemical mechanisms. In the limit of irreversible aggregation, infinitely strong interparticle bonds lead to diffusion-limited cluster aggregation (DLCA). This is understood as a purely kinetic phenomenon that can form solid-like gels at arbitrarily low particle volume fraction. Far more important technologically are systems with weaker attractions, where gel formation requires higher volume fractions. Numerous scenarios for gelation have been proposed, including DLCA, kinetic or dynamic arrest, phase separation, percolation and jamming. No consensus has emerged and, despite its ubiquity and significance, gelation is far from understood-even the location of the gelation phase boundary is not agreed on. Here we report experiments showing that gelation of spherical particles with isotropic, short-range attractions is initiated by spinodal decomposition; this thermodynamic instability triggers the formation of density fluctuations, leading to spanning clusters that dynamically arrest to create a gel. This simple picture of gelation does not depend on microscopic system-specific details, and should thus apply broadly to any particle system with short-range attractions. Our results suggest that gelation-often considered a purely kinetic phenomenon-is in fact a direct consequence of equilibrium liquid-gas phase separation. Without exception, we observe gelation in all of our samples predicted by theory and simulation to phase-separate; this suggests that it is phase separation, not percolation, that corresponds to gelation in models for attractive spheres.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Peter J -- Zaccarelli, Emanuela -- Ciulla, Fabio -- Schofield, Andrew B -- Sciortino, Francesco -- Weitz, David A -- England -- Nature. 2008 May 22;453(7194):499-503. doi: 10.1038/nature06931.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Cambridge, Massachusetts 02138, USA. plu@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497820" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2007-02-27
    Description: The conventional view holds that girih (geometric star-and-polygon, or strapwork) patterns in medieval Islamic architecture were conceived by their designers as a network of zigzagging lines, where the lines were drafted directly with a straightedge and a compass. We show that by 1200 C.E. a conceptual breakthrough occurred in which girih patterns were reconceived as tessellations of a special set of equilateral polygons ("girih tiles") decorated with lines. These tiles enabled the creation of increasingly complex periodic girih patterns, and by the 15th century, the tessellation approach was combined with self-similar transformations to construct nearly perfect quasi-crystalline Penrose patterns, five centuries before their discovery in the West.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Peter J -- Steinhardt, Paul J -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1106-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Harvard University, Cambridge, MA 02138, USA. plu@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17322056" target="_blank"〉PubMed〈/a〉
    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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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-05-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Peter J -- Steinhardt, Paul J -- New York, N.Y. -- Science. 2007 May 18;316(5827):981-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17510346" target="_blank"〉PubMed〈/a〉
    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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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2004-06-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Peter J -- New York, N.Y. -- Science. 2004 Jun 11;304(5677):1638.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Harvard University, 17 Oxford Street, Cambridge, MA 02138, USA. plu@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15192220" target="_blank"〉PubMed〈/a〉
    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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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-06-06
    Description: Quasicrystals are solids whose atomic arrangements have symmetries that are forbidden for periodic crystals, including configurations with fivefold symmetry. All examples identified to date have been synthesized in the laboratory under controlled conditions. Here we present evidence of a naturally occurring icosahedral quasicrystal that includes six distinct fivefold symmetry axes. The mineral, an alloy of aluminum, copper, and iron, occurs as micrometer-sized grains associated with crystalline khatyrkite and cupalite in samples reported to have come from the Koryak Mountains in Russia. The results suggest that quasicrystals can form and remain stable under geologic conditions, although there remain open questions as to how this mineral formed naturally.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bindi, Luca -- Steinhardt, Paul J -- Yao, Nan -- Lu, Peter J -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1306-9. doi: 10.1126/science.1170827.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Museo di Storia Naturale, Sezione di Mineralogia, Universita degli Studi di Firenze, Firenze I-50121, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498165" target="_blank"〉PubMed〈/a〉
    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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  • 8
    Publication Date: 2013-04-17
    Description: DNA binding proteins find their cognate sequences within genomic DNA through recognition of specific chemical and structural features. Here we demonstrate that high-resolution DNase I cleavage profiles can provide detailed information about the shape and chemical modification status of genomic DNA. Analyzing millions of DNA backbone hydrolysis events on naked...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Bioorganic and Medicinal Chemistry 2 (1994), S. 7-13 
    ISSN: 0968-0896
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Nature 440, 528–534 (2006) During editing to meet Nature’s limits on length, we removed a reference to an earlier paper1 reporting that the prolyl isomerase Pin1 promotes production of Alzheimer’s ...
    Type of Medium: Electronic Resource
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