Research Topics
Genomes and Genes | Cecile PickartSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
Polyubiquitin chains: polymeric protein signalsCecile M Pickart
Department of Biochemistry and Molecular Biology, Johns Hopkins University, Baltimore, MD 21205, USA
Curr Opin Chem Biol 8:610-6. 2004..Although the molecular mechanisms governing specificity in chain synthesis and recognition are still incompletely understood, the scope of signaling by polyubiquitin chains is likely to be broader than originally envisioned...- Ubiquitin: structures, functions, mechanismsCecile M Pickart
Department of Biochemistry and Molecular Biology Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
Biochim Biophys Acta 1695:55-72. 2004..This article reviews the basic biochemistry of these protein conjugation reactions, focusing on ubiquitin itself and emphasizing recent insights into mechanism and specificity... - Proteasomes and their kin: proteases in the machine ageCecile M Pickart
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205, USA
Nat Rev Mol Cell Biol 5:177-87. 2004 - Back to the future with ubiquitinCecile M Pickart
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Cell 116:181-90. 2004..This perspective discusses the impact of those papers and highlights some of the subsequent insights that have led to our current appreciation of the breadth of ubiquitin-mediated signaling... 
Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesisMin Wang
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
EMBO J 24:4324-33. 2005..A small region near the N-terminus of the conserved HECT domain helps to bring about this functional distinction. Thus, a given HECT domain can specify both the linkage of a polyubiquitin chain and the mechanism of its assembly...- Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1Tao Wang
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Biol 386:1011-23. 2009..Bidentate binding may be a general strategy used to achieve linkage-specific deubiquitination... - Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formationMichael J Eddins
Department of Biophysics and Biophysical Chemistry and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nat Struct Mol Biol 13:915-20. 2006..The structure reveals the key role of Mms2 in allowing selective insertion of Lys63 into the Ubc13 active site and suggests a molecular model for polyubiquitin chain elongation... - Rad23 ubiquitin-associated domains (UBA) inhibit 26 S proteasome-catalyzed proteolysis by sequestering lysine 48-linked polyubiquitin chainsShahri Raasi
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Biol Chem 278:8951-9. 2003..These results place constraints on the mechanism(s) by which UbL-UBA proteins promote proteasome-catalyzed proteolysis and reveal new properties of UBA domains... - Proteolytic targeting of transcriptional regulator TIP120B by a HECT domain E3 ligaseJianxin You
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Biol Chem 278:23369-75. 2003..KIAA10 and TIP120B are both highly expressed in human skeletal muscle, suggesting that KIAA10 may regulate TIP120B homeostasis specifically in this tissue... - K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1Eric M Cooper
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
EMBO J 28:621-31. 2009..Our results suggest that specificity for K63-linked polyubiquitin is a common property of the JAMM/MPN+ family of DUBs... - Functional dissection of a HECT ubiquitin E3 ligaseJin Ying Lu
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Cell Proteomics 7:35-45. 2008..Finally we showed that the localization of another newly identified substrate, Rnr2, is Rsp5-dependent. We believe that our approach constitutes a paradigm for the functional dissection of an enzyme with pleiotropic effects... - A proteasomal ATPase subunit recognizes the polyubiquitin degradation signalY Amy Lam
Department of Biochemistry and Molecular Biology, School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
Nature 416:763-7. 2002..Our results suggest that productive recognition of the proteolytic signal, as well as proteasome assembly and substrate unfolding, are ATP-dependent events... - Crystal structure and solution NMR studies of Lys48-linked tetraubiquitin at neutral pHMichael J Eddins
Department of Biophysics and Biophysical Chemistry and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Mol Biol 367:204-11. 2007..The structure provides a basis for understanding Lys48-linked polyubiquitin recognition under physiological conditions... - Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23AShahri Raasi
Department of Biochemistry and Molecular Biology Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
J Mol Biol 341:1367-79. 2004..Our findings provide new insights into polyubiquitin chain recognition and set the stage for future structural investigations of UBA/polyubiquitin complexes... - Diverse polyubiquitin interaction properties of ubiquitin-associated domainsShahri Raasi
Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA
Nat Struct Mol Biol 12:708-14. 2005..Conversely, non-UBA sequences can modulate the interaction properties of a UBA domain... - Chemical and genetic strategies for manipulating polyubiquitin chain structureSara Volk
Department of Biochemistry and Molecular Biology, Johns Hopkins University, Baltimore, Maryland, USA
Methods Enzymol 399:3-20. 2005..In this chapter, we outline chemical and genetic strategies that can be used to deduce (or control) the structures of polyubiquitin chains in vitro and in living cells... - Molecular determinants of polyubiquitin linkage selection by an HECT ubiquitin ligaseMin Wang
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
EMBO J 25:1710-9. 2006.... - Ubiquitin binding site of the ubiquitin E2 variant (UEV) protein Mms2 is required for DNA damage tolerance in the yeast RAD6 pathwayColleen Tsui
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Biol Chem 280:19829-35. 2005..These results suggest that the ubiquitin binding site of Mms2 is necessary for error-free lesion bypass in the RAD6 pathway and provide new insights into ubiquitin recognition by UEV proteins... - Identification of protein ubiquitylation by electrospray ionization tandem mass spectrometric analysis of sulfonated tryptic peptidesDongxia Wang
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Anal Chem 78:3681-7. 2006..The method is demonstrated by the analysis of three ubiquitin-conjugated proteins using LC/MS/MS... - The ubiquitin-proteasome pathway in Parkinson's disease and other neurodegenerative diseasesChristopher A Ross
Johns Hopkins University School of Medicine, Division of Neurobiology, Department of Psychiatry, Ross Research Building, Room 618, 720 Rutland Avenue, Baltimore, MD 21205, USA
Trends Cell Biol 14:703-11. 2004..However, the exact molecular connections between these systems and pathogenesis remain uncertain and controversial. In this article, we summarize the state of current knowledge, focusing on important unresolved questions... - Synthesis of free and proliferating cell nuclear antigen-bound polyubiquitin chains by the RING E3 ubiquitin ligase Rad5Candice M Carlile
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Biol Chem 284:29326-34. 2009..These findings indicate that Rad5-mediated recognition of monoUb-PCNA in vivo is likely to depend upon interactions with additional factors at stalled replication forks... - A conserved catalytic residue in the ubiquitin-conjugating enzyme familyPei Ying Wu
Department of Biochemistry and Molecular Biology Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
EMBO J 22:5241-50. 2003..We propose that the conserved asparagine side chain stabilizes the oxyanion intermediate formed during lysine attack. The E2 asparagine is the first non-covalent catalytic group to be proposed in any Ub conjugation factor... - Ubiquitin chain synthesisShahri Raasi
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkinds University, Baltimore, MD, USA
Methods Mol Biol 301:47-55. 2005..Individual chains are then deblocked and joined in another round of reaction. Successive rounds of deblocking and synthesis can give rise to a chain of any desired length... - Controlled synthesis of polyubiquitin chainsCecile M Pickart
Department of Biochemistry and Molecular Biology, Johns Hopkins University, Baltimore, Maryland, USA
Methods Enzymol 399:21-36. 2005..Individual chains are then deblocked and joined in another round of reaction. Successive rounds of deblocking and synthesis give rise to a chain of the desired length... - An arsenite-inducible 19S regulatory particle-associated protein adapts proteasomes to proteotoxicityAriel Stanhill
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
Mol Cell 23:875-85. 2006..These features include enhanced cleavage of peptide substrates and suggest that AIRAP adapts the cell's core protein degradation machinery to counteract proteotoxicity induced by an environmental toxin... - Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrateMingsheng Zhang
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
EMBO J 22:1488-96. 2003.... - E2-25K mediates US11-triggered retro-translocation of MHC class I heavy chains in a permeabilized cell systemDennis Flierman
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Proc Natl Acad Sci U S A 103:11589-94. 2006..We conclude that in permeabilized, US11-expressing cells polyubiquitination of the HC substrate can be catalyzed by E2-25K, perhaps in cooperation with the ligase MARCHVII/axotrophin... - DNA repair: right on target with ubiquitinCecile M Pickart
Nature 419:120-1. 2002 - Beginning at the end with SUMOMichael J Matunis
Nat Struct Mol Biol 12:565-6. 2005
Research Grants
- BIACORE 3000 BiosensorCecile Pickart; Fiscal Year: 2004..In recognition of this fact, the Bloomberg School of Public Health has made a substantial commitment to the long-term operation and maintenance of the Biacore 3000 ..
- DNA REPAIR SIGNALING BY NOVEL POLYUBIQUITIN CHAINSCecile Pickart; Fiscal Year: 2003..abstract_text> ..
- PROTEOLYTIC SIGNALING BY POLYUBIQUITIN CHAINSCecile Pickart; Fiscal Year: 2003..The results of this research will also shed new light on the mechanism of the 26S proteasome, which is the major entity for regulatory proteolysis in eukaryotic cells. ..
- ASCB Conf:Nontraditional Functions of Ubiquitin and UbLsCecile Pickart; Fiscal Year: 2002..There will also be a poster session. The format of the Conference, and its small size, are designed to foster interactions among the 200 participants. ..
- PROTEOLYTIC SIGNALING BY POLYUBIQUITIN CHAINSCecile Pickart; Fiscal Year: 2001..This hypothesis will be treated in the proposed research through analysis of the structure and recognition of polyubiquitin chains that are linked through Lys63. ..
- DNA REPAIR SIGNALING BY NOVEL POLYUBIQUITIN CHAINSCecile Pickart; Fiscal Year: 2005..abstract_text> ..