Philip ColeSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
Protein tyrosine kinases Src and Csk: a tail's talePhilip A Cole
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Curr Opin Chem Biol 7:580-5. 2003..The molecular basis of the specificity of Csk targeting the Src tail appears to involve both local and long-range interactions and illustrates the complexity of selective targeting in post-translational modification...- Chemical approaches to reversible protein phosphorylationPhilip A Cole
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
Acc Chem Res 36:444-52. 2003.... 
Chemical probes for histone-modifying enzymesPhilip A Cole
Department of Pharmacology and Molecular Sciences, Johns Hopkins UniversitySchool of Medicine, 75 N Wolfe Street, Baltimore, Maryland 21205, USA
Nat Chem Biol 4:590-7. 2008..We highlight applications of compounds to mechanistic and functional studies involving these enzymes and discuss future challenges regarding target specificity and general utility...- LSD1 and the chemistry of histone demethylationJeffrey C Culhane
Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, MD 21205, United States
Curr Opin Chem Biol 11:561-8. 2007.... - Site-specific introduction of an acetyl-lysine mimic into peptides and proteins by cysteine alkylationRong Huang
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Am Chem Soc 132:9986-7. 2010..We also use this approach to obtain functional evidence that acetylation of CK2 protein kinase on Lys102 can stimulate its catalytic activity... - Protein kinase structure and function analysis with chemical toolsKui Shen
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Biochim Biophys Acta 1754:65-78. 2005..They have also been used to characterize the cellular regulation of the melatonin rhythm enzyme by phosphorylation... - Bisubstrate analog probes for the insulin receptor protein tyrosine kinase: molecular yardsticks for analyzing catalytic mechanism and inhibitor designAliya C Hines
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Bioorg Chem 33:285-97. 2005..Taken together, these results suggest that a combination of mechanism-based design and empirical synthetic manipulation will be necessary in producing optimized protein kinase bisubstrate analog inhibitors... - The chemical biology of protein phosphorylationMary Katherine Tarrant
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Annu Rev Biochem 78:797-825. 2009..Exciting advances in our understanding of protein phosphorylation have been obtained with these chemical biology approaches, but continuing opportunities for technological innovation remain... - Selective HAT inhibitors as mechanistic tools for protein acetylationYujun Zheng
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, USA
Methods Enzymol 376:188-99. 2004 - Cellular stability of serotonin N-acetyltransferase conferred by phosphonodifluoromethylene alanine (Pfa) substitution for Ser-205Weiping Zheng
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 280:10462-7. 2005.... - Efficient synthesis of phosphorylated prodrugs with bis(POM)-phosphoryl chlorideYousang Hwang
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe St. Baltimore, Maryland 21205, USA
Org Lett 6:1555-6. 2004..The preparation of various bis-pivaloyloxymethyl (POM) phosphate triesters was accomplished in moderate to good yields with the use of bis(POM) phosphoryl chloride under mild conditions... - Multiple roles for acetylation in the interaction of p300 HAT with ATF-2Balasubramanyam Karanam
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
Biochemistry 46:8207-16. 2007..Taken together, these studies suggest multiple roles for protein acetylation in the regulation of transcription by p300/CBP and ATF-2... - Design, synthesis, and characterization of an ATP-peptide conjugate inhibitor of protein kinase AAliya C Hines
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe St. Baltimore, MD 21205, USA
Bioorg Med Chem Lett 14:2951-4. 2004.... - Protein semisynthesis and expressed protein ligation: chasing a protein's tailDirk Schwarzer
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Curr Opin Chem Biol 9:561-9. 2005..Site-specific incorporation of unnatural amino acids, biophysical probes and post-translational modifications in proteins have led to new insights into enzyme mechanisms, protein folding, ion channel function, translation and signaling... - Kinetic and mass spectrometric analysis of p300 histone acetyltransferase domain autoacetylationBalasubramanyam Karanam
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Biol Chem 281:40292-301. 2006..Several of these rapid autoacetylation sites correlate with an acetyltransferase-activating function based on prior mutagenesis analysis... - A mechanism-based inactivator for histone demethylase LSD1Jeffrey C Culhane
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Am Chem Soc 128:4536-7. 2006..Compound 1 is thus a selective, mechanism-based inactivator of LSD1 and is likely to serve as a useful tool in the study of histone modifications and chromatin remodeling... - Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitorErin M Bowers
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Chem Biol 17:471-82. 2010..Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target... - Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitorsVatsala Sagar
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA
Bioorg Med Chem 12:3383-90. 2004..These structure-activity studies allow for a greater understanding of the optimal requirements for potent inhibition of HAT enzymes and pave the way for a novel class of anti-cancer therapeutics... - Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutralWeiping Zheng
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Bioorg Chem 31:398-411. 2003..Since AANAT belongs to the GCN5-related N-acetyltransferase (GNAT) superfamily, our experimental strategies should find applications for other acetyltransferases... - Serotonin N-acetyltransferase: mechanism and inhibitionWeiping Zheng
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Curr Med Chem 9:1187-99. 2002..This review will focus on the efforts toward developing in vitro and in vivo AANAT inhibitors, including basic mechanistic studies on AANAT, which have played an important role in design... - Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociationDongqing Wang
Endocrinology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
Mol Endocrinol 23:600-9. 2009.... - Development of photo-crosslinking reagents for protein kinase-substrate interactionsKeykavous Parang
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
FEBS Lett 520:156-60. 2002..The crosslinked adducts can be readily cleaved by phosphodiesterase which supports the model for crosslinking and provides a simple method to deconvolute the linked protein partners... - The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligationZhongsen Zhang
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 278:4668-74. 2003.... - Comparative analysis of small molecules and histone substrate analogues as LSD1 lysine demethylase inhibitorsJeffrey C Culhane
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Am Chem Soc 132:3164-76. 2010..We show that phenelzine can block histone H3K4Me demethylation in cells, validating it as a pharmacologic tool and potential lead structure for anticancer therapy... - Analysis of protein kinase autophosphorylation using expressed protein ligation and computational modelingKerry A Pickin
Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, Maryland 21210, USA
J Am Chem Soc 130:5667-9. 2008..This approach could be applied to other autoprocessing enzymes by exploiting appropriate transition state analogue motifs in the context of protein semisynthesis... - Substrate conformational restriction and CD45-catalyzed dephosphorylation of tail tyrosine-phosphorylated Src proteinDongxia Wang
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Biol Chem 277:40428-33. 2002..Taken together, these results suggest how activation of Src family member signaling pathways by CD45 may be influenced by the presence or absence of ligand interactions remote from the tail... - Protein tyrosine kinase-substrate interactionsRon Bose
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Curr Opin Struct Biol 16:668-75. 2006..These PTK co-crystal structures reveal both conserved and specialized features of recognition that probably contribute to substrate selection and the individual functions of these key enzymes... - Electrophilic tuning of the chemoprotective natural product sulforaphaneYoung Hoon Ahn
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 107:9590-5. 2010..We further show in living cells that a sulfoxythiocarbamate analog can label Keap1 on several key cysteine residues as well as other cellular proteins offering new insights into the mechanism of chemoprotection... - Mechanistic analysis of a suicide inactivator of histone demethylase LSD1Lawrence M Szewczuk
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Biochemistry 46:6892-902. 2007..Using 1-Btn, it was feasible to selectively pull down spiked and endogenous LSD1 from HeLa cell nuclear extracts, setting the stage for activity-based demethylase proteomics... - Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesisKannan R Karukurichi
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
J Am Chem Soc 132:1222-3. 2010.... - A lock on phosphotyrosine signalingKathryn E Muratore
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
ACS Chem Biol 2:454-6. 2007..A new technique allows site-specific incorporation of a non-hydrolyzable phosphotyrosine analogue into recombinant proteins, providing a new strategy for research in this important area... - A selective chemical probe for coenzyme A-requiring enzymesYousang Hwang
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Angew Chem Int Ed Engl 46:7621-4. 2007 - Protein phosphorylation by semisynthesis: from paper to practiceLawrence M Szewczuk
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Methods Enzymol 462:1-24. 2009..This chapter outlines the general methods and considerations for designing and carrying out phosphoprotein semisynthetic projects... - De novo discovery of serotonin N-acetyltransferase inhibitorsLawrence M Szewczuk
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
J Med Chem 50:5330-8. 2007..Overall, this study demonstrates the feasibility of using virtual screening to identify small molecules that are selective inhibitors of AANAT... - In vitro enzymatic characterization of near full length EGFR in activated and inhibited statesChen Qiu
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21204, USA
Biochemistry 48:6624-32. 2009..The potencies of the small molecule EGFR kinase inhibitors erlotinib and lapatinib for various forms of EGFR were measured, and the therapeutic and mechanistic implications of these results considered... - Structure and chemistry of the p300/CBP and Rtt109 histone acetyltransferases: implications for histone acetyltransferase evolution and functionLing Wang
Department of Pharmacology and Molecular Sciences, Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Curr Opin Struct Biol 18:741-7. 2008..These studies also point to the importance of regulatory loops within HATs and autoacetylation in HAT function. Implications for future studies are discussed... - Mechanism of activation and inhibition of the HER4/ErbB4 kinaseChen Qiu
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Structure 16:460-7. 2008..These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members... - Phosphoproteomic analysis of Her2/neu signaling and inhibitionRon Bose
Department of Pharmacology, McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 103:9773-8. 2006..Network modeling, which combined phosphoproteomic results with literature-curated protein-protein interaction data, was used to suggest roles for some of the previously unidentified Her2 signaling proteins... - Structural analysis of a highly acetylated protein using a curved-field reflectron mass spectrometerDongxia Wang
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proteomics 5:2288-96. 2005..Using MS and MS/MS, we were able to characterize both the unmodified and acetylated tryptic peptides covering more than 82% of the protein... - Chemical dissection of the effects of tyrosine phosphorylation of SHP-2Wei Lu
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA
Biochemistry 42:5461-8. 2003..This allowed for a systematic analysis of intermolecular autodephosphorylation of SHP-2, which revealed how conformational plasticity can modulate phosphotyrosine stability... - Proton demand inversion in a mutant protein tyrosine kinase reactionDaniel M Williams
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Room 316, Hunterian Building, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
J Am Chem Soc 124:5956-7. 2002..These combined results argue against a hydroxy nucleophile-to-phosphate proton transfer occurring prior to an associative transition state of phosphoryl transfer... - Fluorescence analysis of a dynamic loop in the PCAF/GCN5 histone acetyltransferaseYujun Zheng
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Biochemistry 44:10501-9. 2005..The relevance of loop dynamics to PCAF/GCN5 catalysis and substrate specificity are discussed... - Chemical rescue of a mutant enzyme in living cellsYingfeng Qiao
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Science 311:1293-7. 2006..Rescue of R388A cellular Src provided insights into the mitogen-activated protein kinase pathway. This chemical rescue approach will likely have many applications in cell signaling... - Negative regulation of a protein tyrosine phosphatase by tyrosine phosphorylationDirk Schwarzer
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Am Chem Soc 128:4192-3. 2006..These findings suggest the first example of a tyrosine phosphatase that is inhibited by tyrosine phosphorylation and provide a new model for the regulation of LMW-PTP and its role in cell adhesion... - Regulation of the p300 HAT domain via a novel activation loopPaul R Thompson
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nat Struct Mol Biol 11:308-15. 2004..We therefore propose that this autoregulatory loop could influence the impact of p300 on a wide variety of signaling and transcriptional events... - Structure of the GCN5 histone acetyltransferase bound to a bisubstrate inhibitorArienne N Poux
The Wistar Institute, and Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 99:14065-70. 2002..The structure also provides a structural scaffold for the design of HAT-specific inhibitors that may have therapeutic applications for the treatment of HAT-mediated cancers... - Designing bisubstrate analog inhibitors for protein kinasesKeykavous Parang
Department of Biomedical Sciences, College of Pharmacy, University of Rhode Island, 41 Lower College Road, Kingston, RI 02881, USA
Pharmacol Ther 93:145-57. 2002..Emphasis is given to bivalent approaches, with an interpretation of what has been learned from more and less successful examples. Future challenges in this area are also highlighted... - Structural basis of histone demethylation by LSD1 revealed by suicide inactivationMaojun Yang
Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390, USA
Nat Struct Mol Biol 14:535-9. 2007..The unusual backbone conformation of LSD1-bound H3 suggests a strategy for designing potent LSD1 inhibitors with therapeutic potential... - Transcriptional activation by thyroid hormone receptor-beta involves chromatin remodeling, histone acetylation, and synergistic stimulation by p300 and steroid receptor coactivatorsKathleen C Lee
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
Mol Endocrinol 17:908-22. 2003..Our studies highlight the functional importance of chromatin in transcriptional control and further define the molecular mechanisms by which the SRC and p300 coactivators facilitate transcriptional activation by liganded TRbeta... - Histone demethylation mediated by the nuclear amine oxidase homolog LSD1Yujiang Shi
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Cell 119:941-53. 2004..The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases... - Reading and function of a histone code involved in targeting corepressor complexes for repressionHo Geun Yoon
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Mol Cell Biol 25:324-35. 2005..Our studies provide an in vivo example that a histone code is not read independently but is recognized in the context of other interactions... - Tax recruitment of CBP/p300, via the KIX domain, reveals a potent requirement for acetyltransferase activity that is chromatin dependent and histone tail independentSara A Georges
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA
Mol Cell Biol 23:3392-404. 2003..Significantly, these observations reveal the presence of one or more CBP/p300 acetyltransferase targets that function specifically on chromatin templates, are independent of the histone tails, and are critical to Tax transactivation... - DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genesAntonio Costanzo
Laboratory of Gene Expression, Fondazione Andrea Cesalpino, University of Rome La Sapienza, 00161, Rome, Italy
Mol Cell 9:175-86. 2002..Our results suggest that DNA damage-induced acetylation potentiates the apoptotic function of p73 by enhancing the ability of p73 to selectively activate the transcription of proapoptotic target genes... - Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytesDebdutta Bandyopadhyay
Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
Cancer Res 62:6231-9. 2002..Together, these results provide evidence for the essential role of p300 in the regulation of proliferation and senescence in cells from melanocytic origin... - The role of the phospho-CDK2/cyclin A recruitment site in substrate recognitionKin Yip Cheng
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom
J Biol Chem 281:23167-79. 2006..The notion of a flexible linker between the sites, which must have more than a minimal number of residues, provides an explanation for recognition and discrimination against different substrates... - Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin templateHanxin Lu
Virus Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Cell Biol 22:4450-62. 2002..Finally, using the chromatin immunoprecipitation assay, we provide the first direct experimental evidence that p300 and CBP are associated with the HTLV-1 long terminal repeat in vivo... - X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibitionEva Wolf
Laboratories of Molecular Biophysics, The Rockefeller University, New York, NY 10021, USA
J Mol Biol 317:215-24. 2002..Our findings may ultimately lead to the design of analogs with improved AANAT inhibitory properties for in vivo applications... - A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcriptionZhi-Qing Huang
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
EMBO J 22:2146-55. 2003.... - Structural basis for the recognition of c-Src by its inactivator CskNicholas M Levinson
Department of Molecular and Cell Biology, Department of Chemistry, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences QB3, University of California, Berkeley, Berkeley, CA 94720, USA
Cell 134:124-34. 2008..Csk cannot phosphorylate substrates that lack this docking mechanism because the conventional substrate binding site used by most tyrosine kinases to recognize substrates is destabilized in Csk by a deletion in the activation loop... - An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptorXuewu Zhang
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, 94720, USA
Cell 125:1137-49. 2006..The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization... - A Src-like inactive conformation in the abl tyrosine kinase domainNicholas M Levinson
Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA
PLoS Biol 4:e144. 2006..Our results suggest that interconversion between distinctly different inactive conformations is a characteristic feature of the Abl kinase domain... - Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamineMaojun Yang
Departments of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390, USA
Biochemistry 46:8058-65. 2007..This study thus provides the basis for designing more potent inhibitors of LSD1 that contain substitutions on the phenyl ring of PCPA to fully engage neighboring residues... - p300/CBP-associated factor drives DEK into interchromatin granule clustersJoanne Cleary
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan 48109 0640, USA
J Biol Chem 280:31760-7. 2005..These findings also suggest that DEK-associated malignancies and autoimmune diseases might be amenable to treatment with agents that alter acetylation... - Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger proteinFabien Guidez
Section of Haemato oncology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
Mol Cell Biol 25:5552-66. 2005..Taken together, our results indicate that a histone deacetylase-dependent transcriptional repressor can be positively regulated through acetylation and point to an unexpected role of a coactivator protein in transcriptional repression... - TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcriptionNiall S Kenneth
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
Proc Natl Acad Sci U S A 104:14917-22. 2007..The selective acetylation of histone H3 distinguishes pol III activation by c-Myc from mechanisms observed in other systems... 
The structural basis of protein acetylation by the p300/CBP transcriptional coactivatorXin Liu
Program in Gene Expression and Regulation, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
Nature 451:846-50. 2008..Several disease-associated mutations can also be readily accounted for by the p300 HAT structure. These studies pave the way for new epigenetic therapies involving modulation of p300/CBP HAT activity...- Acetylation of Tat defines a cyclinT1-independent step in HIV transactivationKatrin Kaehlcke
Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
Mol Cell 12:167-76. 2003..We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II... - Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBPYong Tang
Program in Gene Expression and Regulation, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
Nat Struct Mol Biol 15:738-45. 2008..The structure reveals a buried autoacetylated lysine residue that we show is also acetylated in the Rtt109 protein purified from yeast cells. Implications for understanding histone substrate and chaperone binding by Rtt109 are discussed... - Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interfaceXuewu Zhang
Department of Molecular and Cell Biology, and Howard Hughes Medical Institute, California Institute for Quantitative Sciences, University of California, Berkeley, California 94720, USA
Nature 450:741-4. 2007..We show that signalling by EGFR molecules that contain constitutively active kinase domains still requires formation of the asymmetric dimer, underscoring the importance of dimer interface blockage in MIG6-mediated inhibition...
Research Grants
- Mechanisms & Inhibition of Histone AcetyltransferasesPhilip Cole; Fiscal Year: 2007..Selective inhibitors of HAT enzymes may be useful in the treatment of cancer, HIV, and other diseases related to the dysregulation of protein acetylation. ..
- Serotonin N-acethyltransferase Regulation & InhibitionPhilip Cole; Fiscal Year: 2007..It is expected that these studies will lead to an increase in our understanding about the role of melatonin in health and disease and that newly designed inhibitors may serve as lead agents for the treatment of sleep and mood disorders. ..
- Chemical Approaches to Protein PhosphorylationPhilip Cole; Fiscal Year: 2007....
- Histone Modification Mechanisms and InhibitionPhilip A Cole; Fiscal Year: 2010..Insights obtained from this research plan could lead to new therapeutic strategies for cancer, diabetes, immune disorders, and neuropsychiatric conditions. ..
- Chemical Approaches to Protein PhosphorylationPhilip A Cole; Fiscal Year: 2010....
- Chemical Approaches to Protein PhosphorylationPhilip Cole; Fiscal Year: 2006..The new approaches to protein kinase inhibitors may ultimately provide lead agents for the treatment of cancer, immune system-related diseases, and cardiovascular pathologies. ..
- ACETYLTRANSFERASE INHIBITION AND SELECTIVITYPhilip Cole; Fiscal Year: 2004..Selective inhibitors of HAT enzymes may be useful in the treatment of cancer, HIV, and other diseases related to the dysregulation of gene expression. ..
- Serotonin N Acetyltransferase Mechanism and InhibitionPhilip Cole; Fiscal Year: 2004....
- Histone Modification Mechanisms and InhibitionPhilip A Cole; Fiscal Year: 2010..Insights obtained from this research plan could lead to new therapeutic strategies for cancer, diabetes, immune disorders, and neuropsychiatric conditions. ..