Philip Cole

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. ncbi request reprint Protein tyrosine kinases Src and Csk: a tail's tale
    Philip 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
  2. ncbi request reprint Chemical approaches to reversible protein phosphorylation
    Philip 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
  3. pmc Chemical probes for histone-modifying enzymes
    Philip 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
  4. pmc LSD1 and the chemistry of histone demethylation
    Jeffrey 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
  5. pmc Site-specific introduction of an acetyl-lysine mimic into peptides and proteins by cysteine alkylation
    Rong 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
  6. ncbi request reprint Protein kinase structure and function analysis with chemical tools
    Kui Shen
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Biochim Biophys Acta 1754:65-78. 2005
  7. ncbi request reprint Bisubstrate analog probes for the insulin receptor protein tyrosine kinase: molecular yardsticks for analyzing catalytic mechanism and inhibitor design
    Aliya C Hines
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Bioorg Chem 33:285-97. 2005
  8. pmc The chemical biology of protein phosphorylation
    Mary Katherine Tarrant
    Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
    Annu Rev Biochem 78:797-825. 2009
  9. ncbi request reprint Selective HAT inhibitors as mechanistic tools for protein acetylation
    Yujun Zheng
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, USA
    Methods Enzymol 376:188-99. 2004
  10. ncbi request reprint Cellular stability of serotonin N-acetyltransferase conferred by phosphonodifluoromethylene alanine (Pfa) substitution for Ser-205
    Weiping 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

Research Grants

Collaborators

Detail Information

Publications69

  1. ncbi request reprint Protein tyrosine kinases Src and Csk: a tail's tale
    Philip 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...
  2. ncbi request reprint Chemical approaches to reversible protein phosphorylation
    Philip 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
    ....
  3. pmc Chemical probes for histone-modifying enzymes
    Philip 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...
  4. pmc LSD1 and the chemistry of histone demethylation
    Jeffrey 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
    ....
  5. pmc Site-specific introduction of an acetyl-lysine mimic into peptides and proteins by cysteine alkylation
    Rong 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...
  6. ncbi request reprint Protein kinase structure and function analysis with chemical tools
    Kui 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...
  7. ncbi request reprint Bisubstrate analog probes for the insulin receptor protein tyrosine kinase: molecular yardsticks for analyzing catalytic mechanism and inhibitor design
    Aliya 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...
  8. pmc The chemical biology of protein phosphorylation
    Mary 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...
  9. ncbi request reprint Selective HAT inhibitors as mechanistic tools for protein acetylation
    Yujun Zheng
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, USA
    Methods Enzymol 376:188-99. 2004
  10. ncbi request reprint Cellular stability of serotonin N-acetyltransferase conferred by phosphonodifluoromethylene alanine (Pfa) substitution for Ser-205
    Weiping 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
    ....
  11. ncbi request reprint Efficient synthesis of phosphorylated prodrugs with bis(POM)-phosphoryl chloride
    Yousang 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...
  12. pmc Multiple roles for acetylation in the interaction of p300 HAT with ATF-2
    Balasubramanyam 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...
  13. ncbi request reprint Design, synthesis, and characterization of an ATP-peptide conjugate inhibitor of protein kinase A
    Aliya 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
    ....
  14. ncbi request reprint Protein semisynthesis and expressed protein ligation: chasing a protein's tail
    Dirk 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...
  15. ncbi request reprint Kinetic and mass spectrometric analysis of p300 histone acetyltransferase domain autoacetylation
    Balasubramanyam 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...
  16. ncbi request reprint A mechanism-based inactivator for histone demethylase LSD1
    Jeffrey 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...
  17. pmc Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor
    Erin 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...
  18. ncbi request reprint Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitors
    Vatsala 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...
  19. ncbi request reprint Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral
    Weiping 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...
  20. ncbi request reprint Serotonin N-acetyltransferase: mechanism and inhibition
    Weiping 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...
  21. pmc Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation
    Dongqing Wang
    Endocrinology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Mol Endocrinol 23:600-9. 2009
    ....
  22. ncbi request reprint Development of photo-crosslinking reagents for protein kinase-substrate interactions
    Keykavous 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...
  23. ncbi request reprint The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligation
    Zhongsen Zhang
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Biol Chem 278:4668-74. 2003
    ....
  24. pmc Comparative analysis of small molecules and histone substrate analogues as LSD1 lysine demethylase inhibitors
    Jeffrey 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...
  25. pmc Analysis of protein kinase autophosphorylation using expressed protein ligation and computational modeling
    Kerry 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...
  26. ncbi request reprint Substrate conformational restriction and CD45-catalyzed dephosphorylation of tail tyrosine-phosphorylated Src protein
    Dongxia 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...
  27. ncbi request reprint Protein tyrosine kinase-substrate interactions
    Ron 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...
  28. pmc Electrophilic tuning of the chemoprotective natural product sulforaphane
    Young 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...
  29. pmc Mechanistic analysis of a suicide inactivator of histone demethylase LSD1
    Lawrence 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...
  30. pmc Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesis
    Kannan 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
    ....
  31. ncbi request reprint A lock on phosphotyrosine signaling
    Kathryn 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...
  32. ncbi request reprint A selective chemical probe for coenzyme A-requiring enzymes
    Yousang 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
  33. pmc Protein phosphorylation by semisynthesis: from paper to practice
    Lawrence 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...
  34. pmc De novo discovery of serotonin N-acetyltransferase inhibitors
    Lawrence 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...
  35. pmc In vitro enzymatic characterization of near full length EGFR in activated and inhibited states
    Chen 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...
  36. pmc Structure and chemistry of the p300/CBP and Rtt109 histone acetyltransferases: implications for histone acetyltransferase evolution and function
    Ling 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...
  37. pmc Mechanism of activation and inhibition of the HER4/ErbB4 kinase
    Chen 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...
  38. pmc Phosphoproteomic analysis of Her2/neu signaling and inhibition
    Ron 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...
  39. ncbi request reprint Structural analysis of a highly acetylated protein using a curved-field reflectron mass spectrometer
    Dongxia 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...
  40. ncbi request reprint Chemical dissection of the effects of tyrosine phosphorylation of SHP-2
    Wei 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...
  41. ncbi request reprint Proton demand inversion in a mutant protein tyrosine kinase reaction
    Daniel 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...
  42. ncbi request reprint Fluorescence analysis of a dynamic loop in the PCAF/GCN5 histone acetyltransferase
    Yujun 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...
  43. ncbi request reprint Chemical rescue of a mutant enzyme in living cells
    Yingfeng 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...
  44. ncbi request reprint Negative regulation of a protein tyrosine phosphatase by tyrosine phosphorylation
    Dirk 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...
  45. ncbi request reprint Regulation of the p300 HAT domain via a novel activation loop
    Paul 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...
  46. pmc Structure of the GCN5 histone acetyltransferase bound to a bisubstrate inhibitor
    Arienne 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...
  47. ncbi request reprint Designing bisubstrate analog inhibitors for protein kinases
    Keykavous 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...
  48. ncbi request reprint Structural basis of histone demethylation by LSD1 revealed by suicide inactivation
    Maojun 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...
  49. ncbi request reprint Transcriptional activation by thyroid hormone receptor-beta involves chromatin remodeling, histone acetylation, and synergistic stimulation by p300 and steroid receptor coactivators
    Kathleen 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...
  50. ncbi request reprint Histone demethylation mediated by the nuclear amine oxidase homolog LSD1
    Yujiang 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...
  51. pmc Reading and function of a histone code involved in targeting corepressor complexes for repression
    Ho 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...
  52. pmc Tax recruitment of CBP/p300, via the KIX domain, reveals a potent requirement for acetyltransferase activity that is chromatin dependent and histone tail independent
    Sara 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...
  53. ncbi request reprint DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes
    Antonio 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...
  54. ncbi request reprint Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytes
    Debdutta 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...
  55. ncbi request reprint The role of the phospho-CDK2/cyclin A recruitment site in substrate recognition
    Kin 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...
  56. pmc Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template
    Hanxin 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...
  57. ncbi request reprint X-ray crystallographic studies of serotonin N-acetyltransferase catalysis and inhibition
    Eva 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...
  58. pmc A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription
    Zhi 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
    ....
  59. pmc Structural basis for the recognition of c-Src by its inactivator Csk
    Nicholas 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...
  60. ncbi request reprint An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor
    Xuewu 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...
  61. pmc A Src-like inactive conformation in the abl tyrosine kinase domain
    Nicholas 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...
  62. ncbi request reprint Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamine
    Maojun 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...
  63. ncbi request reprint p300/CBP-associated factor drives DEK into interchromatin granule clusters
    Joanne 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...
  64. pmc Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein
    Fabien 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...
  65. pmc TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription
    Niall 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...
  66. doi request reprint The structural basis of protein acetylation by the p300/CBP transcriptional coactivator
    Xin 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...
  67. ncbi request reprint Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation
    Katrin 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...
  68. pmc Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP
    Yong 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...
  69. pmc Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface
    Xuewu 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 Grants30

  1. Mechanisms & Inhibition of Histone Acetyltransferases
    Philip 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. ..
  2. Serotonin N-acethyltransferase Regulation & Inhibition
    Philip 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. ..
  3. Chemical Approaches to Protein Phosphorylation
    Philip Cole; Fiscal Year: 2007
    ....
  4. Histone Modification Mechanisms and Inhibition
    Philip 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. ..
  5. Chemical Approaches to Protein Phosphorylation
    Philip A Cole; Fiscal Year: 2010
    ....
  6. Chemical Approaches to Protein Phosphorylation
    Philip 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. ..
  7. ACETYLTRANSFERASE INHIBITION AND SELECTIVITY
    Philip 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. ..
  8. Serotonin N Acetyltransferase Mechanism and Inhibition
    Philip Cole; Fiscal Year: 2004
    ....
  9. Histone Modification Mechanisms and Inhibition
    Philip 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. ..