ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Cancer-associated IDH1 mutations produce 2-hydroxyglutarate (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-11-26
    Description: Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to alpha-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818760/" 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/PMC2818760/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Lenny -- White, David W -- Gross, Stefan -- Bennett, Bryson D -- Bittinger, Mark A -- Driggers, Edward M -- Fantin, Valeria R -- Jang, Hyun Gyung -- Jin, Shengfang -- Keenan, Marie C -- Marks, Kevin M -- Prins, Robert M -- Ward, Patrick S -- Yen, Katharine E -- Liau, Linda M -- Rabinowitz, Joshua D -- Cantley, Lewis C -- Thompson, Craig B -- Vander Heiden, Matthew G -- Su, Shinsan M -- P01 CA104838/CA/NCI NIH HHS/ -- P01 CA104838-05/CA/NCI NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- R01 CA105463-06/CA/NCI NIH HHS/ -- R21 CA128620/CA/NCI NIH HHS/ -- England -- Nature. 2009 Dec 10;462(7274):739-44. doi: 10.1038/nature08617. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Agios Pharmaceuticals, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19935646" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/genetics ; Brain Neoplasms/*genetics/*metabolism/pathology ; Catalytic Domain ; Cell Line ; Crystallography, X-Ray ; Disease Progression ; Enzyme Assays ; Glioma/genetics/metabolism/pathology ; Glutarates/*metabolism ; Histidine/genetics/metabolism ; Humans ; Isocitrate Dehydrogenase/*genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Models, Molecular ; Mutant Proteins/*genetics/*metabolism ; Mutation/genetics ; Protein Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-12-09
    Description: Proteins that directly regulate tumour necrosis factor receptor (TNFR) signalling have critical roles in regulating cellular activation and survival. ABIN-1 (A20 binding and inhibitor of NF-kappaB) is a novel protein that is thought to inhibit NF-kappaB signalling. Here we show that mice deficient for ABIN-1 die during embryogenesis with fetal liver apoptosis, anaemia and hypoplasia. ABIN-1 deficient cells are hypersensitive to tumour necrosis factor (TNF)-induced programmed cell death, and TNF deficiency rescues ABIN-1 deficient embryos. ABIN-1 inhibits caspase 8 recruitment to FADD (Fas-associated death domain-containing protein) in TNF-induced signalling complexes, preventing caspase 8 cleavage and programmed cell death. Moreover, ABIN-1 directly binds polyubiquitin chains and this ubiquitin sensing activity is required for ABIN-1's anti-apoptotic activity. These studies provide insights into how ubiquitination and ubiquitin sensing proteins regulate cellular and organismal survival.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642523/" 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/PMC2642523/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oshima, Shigeru -- Turer, Emre E -- Callahan, Joseph A -- Chai, Sophia -- Advincula, Rommel -- Barrera, Julio -- Shifrin, Nataliya -- Lee, Bettina -- Benedict Yen, T S -- Woo, Tammy -- Malynn, Barbara A -- Ma, Averil -- R01 DK071939/DK/NIDDK NIH HHS/ -- R01 DK071939-01/DK/NIDDK NIH HHS/ -- R01 DK071939-02/DK/NIDDK NIH HHS/ -- R01 DK071939-03/DK/NIDDK NIH HHS/ -- R01 DK071939-04/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Feb 12;457(7231):906-9. doi: 10.1038/nature07575. Epub 2008 Dec 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, S-1057, San Francisco, California 94143-0451, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19060883" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Apoptosis/*physiology ; Cell Line ; DNA-Binding Proteins/chemistry/*metabolism ; Embryonic Development/genetics/*physiology ; Gene Expression Regulation, Developmental ; Humans ; Intracellular Signaling Peptides and Proteins/chemistry/metabolism ; Jurkat Cells ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Sequence Alignment ; Tumor Necrosis Factor-alpha/metabolism ; Ubiquitin/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    Cancer-associated IDH1 mutations produce 2-hydroxyglutarate (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-06-19
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766976/" 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/PMC3766976/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Lenny -- White, David W -- Gross, Stefan -- Bennett, Bryson D -- Bittinger, Mark A -- Driggers, Edward M -- Fantin, Valeria R -- Jang, Hyun Gyung -- Jin, Shengfang -- Keenan, Marie C -- Marks, Kevin M -- Prins, Robert M -- Ward, Patrick S -- Yen, Katharine E -- Liau, Linda M -- Rabinowitz, Joshua D -- Cantley, Lewis C -- Thompson, Craig B -- Vander Heiden, Matthew G -- Su, Shinsan M -- R01 CA105463/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):966. doi: 10.1038/nature09132.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559394" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Glutarates/*metabolism ; Humans ; Isocitrate Dehydrogenase/*genetics ; Mutation/*genetics ; Neoplasms/*physiopathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-03-23
    Description: Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients. Long, double-stranded RNAs were first shown to mediate RNAi in Caenorhabditis elegans, and the potential use of RNAi for human therapy has been demonstrated by the finding that small interfering RNAs (siRNAs; approximately 21-base-pair double-stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response. We are at present conducting the first in-human phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumour biopsies from melanoma patients obtained after treatment show the presence of intracellularly localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is, to our knowledge, a first for systemically delivered nanoparticles of any kind). Furthermore, a reduction was found in both the specific messenger RNA (M2 subunit of ribonucleotide reductase (RRM2)) and the protein (RRM2) levels when compared to pre-dosing tissue. Most notably, we detect the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for an RNAi mechanism from a patient who received the highest dose of the nanoparticles. Together, these data demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855406/" 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/PMC2855406/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, Mark E -- Zuckerman, Jonathan E -- Choi, Chung Hang J -- Seligson, David -- Tolcher, Anthony -- Alabi, Christopher A -- Yen, Yun -- Heidel, Jeremy D -- Ribas, Antoni -- CA U54 119347/CA/NCI NIH HHS/ -- U54 CA119347/CA/NCI NIH HHS/ -- U54 CA119347-04/CA/NCI NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):1067-70. doi: 10.1038/nature08956. Epub 2010 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA. mdavis@cheme.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20305636" target="_blank"〉PubMed〈/a〉
    Keywords: Biopsy ; *Clinical Trials, Phase I as Topic ; *Drug Carriers/administration & dosage/pharmacokinetics ; Drug Delivery Systems ; Gene Knockdown Techniques/*methods ; Humans ; Injections, Intravenous ; Melanoma/drug therapy/enzymology/genetics ; *Nanoparticles/administration & dosage/analysis ; RNA Interference/*drug effects ; RNA, Messenger/analysis/genetics/metabolism ; RNA, Small Interfering/*administration & ; dosage/genetics/*pharmacology/therapeutic use ; Receptors, Transferrin/metabolism ; Ribonucleoside Diphosphate Reductase/biosynthesis/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-12-08
    Description: The human retinoblastoma gene (RB1) encodes a protein (Rb) of 105 kilodaltons that can be phosphorylated. Analysis of Rb metabolism has shown that the protein has a half-life of more than 10 hours and is synthesized at all phases of the cell cycle. Newly synthesized Rb is not extensively phosphorylated (it is "underphosphorylated") in cells in the G0 and G1 phases but is phosphorylated at multiple sites at the G1/S boundary and in S phase. HL-60 cells that were induced to terminally differentiate by various chemicals lost their ability to phosphorylate newly synthesized Rb at multiple sites when cell growth was arrested. These findings suggest that underphosphorylated Rb may restrict cell proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mihara, K -- Cao, X R -- Yen, A -- Chandler, S -- Driscoll, B -- Murphree, A L -- T'Ang, A -- Fung, Y K -- 5P30CA14089/CA/NCI NIH HHS/ -- CA 44754/CA/NCI NIH HHS/ -- EY 07846/EY/NEI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Dec 8;246(4935):1300-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology/Oncology and Ophthalmology, Childrens Hospital of Los Angeles, CA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2588006" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle/*genetics ; Cell Division/drug effects/genetics ; Eye Neoplasms/genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; Interphase/genetics ; Neoplasm Proteins/genetics/*metabolism ; Phosphorylation ; Protein Processing, Post-Translational/drug effects/*genetics ; Retinoblastoma/*genetics ; Tretinoin/pharmacology ; Tumor Cells, Cultured
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-11-03
    Description: During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karnik, Satyajit K -- Chen, Hainan -- McLean, Graeme W -- Heit, Jeremy J -- Gu, Xueying -- Zhang, Andrew Y -- Fontaine, Magali -- Yen, Michael H -- Kim, Seung K -- T32DK007217-32/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):806-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975067" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Diabetes, Gestational/*etiology/metabolism ; Female ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Obesity/metabolism ; Pregnancy ; Prolactin/metabolism ; Proto-Oncogene Proteins/*physiology ; Tumor Cells, Cultured
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    Global protein stability profiling in mammalian cells (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-11-08
    Description: The abundance of cellular proteins is determined largely by the rate of transcription and translation coupled with the stability of individual proteins. Although we know a great deal about global transcript abundance, little is known about global protein stability. We present a highly parallel multiplexing strategy to monitor protein turnover on a global scale by coupling flow cytometry with microarray technology to track the stability of individual proteins within a complex mixture. We demonstrated the feasibility of this approach by measuring the stability of approximately 8000 human proteins and identifying proteasome substrates. The technology provides a general platform for proteome-scale analysis of protein turnover under various physiological and disease conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yen, Hsueh-Chi Sherry -- Xu, Qikai -- Chou, Danny M -- Zhao, Zhenming -- Elledge, Stephen J -- AG11085/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Nov 7;322(5903):918-23. doi: 10.1126/science.1160489.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18988847" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/analysis ; Cell Cycle ; Cell Line ; DNA, Complementary ; Flow Cytometry ; Green Fluorescent Proteins/analysis/metabolism ; Half-Life ; Humans ; Luminescent Proteins/analysis/metabolism ; Oligonucleotide Array Sequence Analysis ; Open Reading Frames ; Proteasome Endopeptidase Complex/*metabolism ; Protein Biosynthesis ; *Protein Stability ; Proteins/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Transcription, Genetic
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-07-23
    Description: Type II topoisomerases (TOP2s) resolve the topological problems of DNA by transiently cleaving both strands of a DNA duplex to form a cleavage complex through which another DNA segment can be transported. Several widely prescribed anticancer drugs increase the population of TOP2 cleavage complex, which leads to TOP2-mediated chromosome DNA breakage and death of cancer cells. We present the crystal structure of a large fragment of human TOP2beta complexed to DNA and to the anticancer drug etoposide to reveal structural details of drug-induced stabilization of a cleavage complex. The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. The analysis of protein-drug interactions provides information applicable for developing an isoform-specific TOP2-targeting strategy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Chyuan-Chuan -- Li, Tsai-Kun -- Farh, Lynn -- Lin, Li-Ying -- Lin, Te-Sheng -- Yu, Yu-Jen -- Yen, Tien-Jui -- Chiang, Chia-Wang -- Chan, Nei-Li -- New York, N.Y. -- Science. 2011 Jul 22;333(6041):459-62. doi: 10.1126/science.1204117.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City 100, Taiwan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21778401" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Catalytic Domain ; Crystallography, X-Ray ; DNA/*chemistry/metabolism ; DNA Topoisomerases, Type II/*chemistry/genetics/metabolism ; DNA-Binding Proteins/*chemistry/genetics/metabolism ; Drug Resistance, Neoplasm ; Etoposide/analogs & derivatives/*chemistry/metabolism/*pharmacology ; Humans ; Models, Molecular ; Mutant Proteins/chemistry/metabolism ; Mutation ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Topoisomerase II Inhibitors/*chemistry/metabolism/*pharmacology
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-04-06
    Description: A number of human cancers harbor somatic point mutations in the genes encoding isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). These mutations alter residues in the enzyme active sites and confer a gain-of-function in cancer cells, resulting in the accumulation and secretion of the oncometabolite (R)-2-hydroxyglutarate (2HG). We developed a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q. A crystal structure of AGI-6780 complexed with IDH2/R140Q revealed that the inhibitor binds in an allosteric manner at the dimer interface. The results of steady-state enzymology analysis were consistent with allostery and slow-tight binding by AGI-6780. Treatment with AGI-6780 induced differentiation of TF-1 erythroleukemia and primary human acute myelogenous leukemia cells in vitro. These data provide proof-of-concept that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Fang -- Travins, Jeremy -- DeLaBarre, Byron -- Penard-Lacronique, Virginie -- Schalm, Stefanie -- Hansen, Erica -- Straley, Kimberly -- Kernytsky, Andrew -- Liu, Wei -- Gliser, Camelia -- Yang, Hua -- Gross, Stefan -- Artin, Erin -- Saada, Veronique -- Mylonas, Elena -- Quivoron, Cyril -- Popovici-Muller, Janeta -- Saunders, Jeffrey O -- Salituro, Francesco G -- Yan, Shunqi -- Murray, Stuart -- Wei, Wentao -- Gao, Yi -- Dang, Lenny -- Dorsch, Marion -- Agresta, Sam -- Schenkein, David P -- Biller, Scott A -- Su, Shinsan M -- de Botton, Stephane -- Yen, Katharine E -- New York, N.Y. -- Science. 2013 May 3;340(6132):622-6. doi: 10.1126/science.1234769. Epub 2013 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Agios Pharmaceuticals, Cambridge, MA 02139-4169, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23558173" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Site ; Antineoplastic Agents/chemistry/metabolism/pharmacology ; Catalytic Domain ; Cell Line, Tumor ; Cell Proliferation ; Cells, Cultured ; Crystallography, X-Ray ; Enzyme Inhibitors/chemistry/metabolism/*pharmacology ; Erythropoiesis/drug effects ; Gene Expression Regulation, Leukemic ; Glutarates/metabolism ; Hematopoiesis/*drug effects ; Humans ; Isocitrate Dehydrogenase/*antagonists & inhibitors/chemistry/*genetics/metabolism ; Leukemia, Erythroblastic, Acute ; Leukemia, Myeloid, Acute/drug therapy/*enzymology/genetics/pathology ; Molecular Targeted Therapy ; Mutant Proteins/antagonists & inhibitors/chemistry/metabolism ; Phenylurea Compounds/chemistry/metabolism/*pharmacology ; Point Mutation ; Protein Multimerization ; Protein Structure, Secondary ; Small Molecule Libraries ; Sulfonamides/chemistry/metabolism/*pharmacology
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-03-28
    Description: Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene, PTEN, that appears to be mutated at considerable frequency in human cancers. In preliminary screens, mutations of PTEN were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas. The predicted PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions. These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, J -- Yen, C -- Liaw, D -- Podsypanina, K -- Bose, S -- Wang, S I -- Puc, J -- Miliaresis, C -- Rodgers, L -- McCombie, R -- Bigner, S H -- Giovanella, B C -- Ittmann, M -- Tycko, B -- Hibshoosh, H -- Wigler, M H -- Parsons, R -- 5R35 CA39829/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Mar 28;275(5308):1943-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, College of Physicians & Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9072974" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Brain Neoplasms/genetics ; Breast Neoplasms/genetics ; Chromosome Mapping ; *Chromosomes, Human, Pair 10 ; Female ; Frameshift Mutation ; *Genes, Tumor Suppressor ; Glioblastoma/genetics ; Humans ; Male ; Microfilament Proteins/chemistry ; Molecular Sequence Data ; *Mutation ; Neoplasm Transplantation ; Neoplasms/*genetics ; PTEN Phosphohydrolase ; *Phosphoric Monoester Hydrolases ; Phosphotyrosine/metabolism ; Prostatic Neoplasms/genetics ; Protein Tyrosine Phosphatases/chemistry/*genetics/physiology ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Sequence Deletion ; Sequence Homology, Amino Acid ; Transplantation, Heterologous ; Tumor Cells, Cultured ; *Tumor Suppressor Proteins
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...