Yigong Shi

Summary

Affiliation: Princeton University
Country: USA

Publications

  1. ncbi Formation of a stable heterodimer between Smad2 and Smad4
    J W Wu
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, New Jersey 08544, USA
    J Biol Chem 276:20688-94. 2001
  2. ncbi Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology
    Eric N Shiozaki
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA
    Trends Biochem Sci 29:486-94. 2004
  3. ncbi Mechanical aspects of apoptosome assembly
    Yigong Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Curr Opin Cell Biol 18:677-84. 2006
  4. ncbi Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein
    Adam Oberstein
    Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    J Biol Chem 282:13123-32. 2007
  5. doi Apoptosome assembly
    Yigong Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey, USA
    Methods Enzymol 442:141-56. 2008
  6. ncbi Apoptosome: the cellular engine for the activation of caspase-9
    Yigong Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544, USA
    Structure 10:285-8. 2002
  7. ncbi Mechanisms of caspase activation and inhibition during apoptosis
    Yigong Shi
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA
    Mol Cell 9:459-70. 2002
  8. ncbi Mechanisms of TGF-beta signaling from cell membrane to the nucleus
    Yigong Shi
    Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA
    Cell 113:685-700. 2003
  9. ncbi A structural view of mitochondria-mediated apoptosis
    Y Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nat Struct Biol 8:394-401. 2001
  10. ncbi Structural insights on Smad function in TGFbeta signaling
    Y Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Bioessays 23:223-32. 2001

Collaborators

Detail Information

Publications85

  1. ncbi Formation of a stable heterodimer between Smad2 and Smad4
    J W Wu
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, New Jersey 08544, USA
    J Biol Chem 276:20688-94. 2001
    ..Importantly, two previous models on the formation of a heterocomplex are incompatible with our observations and other reported evidence...
  2. ncbi Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology
    Eric N Shiozaki
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA
    Trends Biochem Sci 29:486-94. 2004
    ..This inhibition can be removed by Smac/DIABLO during apoptosis. The underlying molecular mechanisms of caspase regulation are discussed in this article...
  3. ncbi Mechanical aspects of apoptosome assembly
    Yigong Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Curr Opin Cell Biol 18:677-84. 2006
    ..This review discusses the assembly, structure and function of the heptameric Apaf-1 apoptosome, the tetrameric CED-4 complex, the octameric Dark apoptosome, and the death-inducing signaling complex (DISC)...
  4. ncbi Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein
    Adam Oberstein
    Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    J Biol Chem 282:13123-32. 2007
    ..We propose that this putative apoptotic function may be linked to the ability of Beclin 1 to suppress tumor formation in mammals...
  5. doi Apoptosome assembly
    Yigong Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey, USA
    Methods Enzymol 442:141-56. 2008
    ..Recent biochemical and structural investigation revealed insights into the assembly and function of the various apoptosomes...
  6. ncbi Apoptosome: the cellular engine for the activation of caspase-9
    Yigong Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544, USA
    Structure 10:285-8. 2002
    ..This structure provides a framework for understanding the activation mechanisms of caspase-9, an important initiator caspase in apoptosis...
  7. ncbi Mechanisms of caspase activation and inhibition during apoptosis
    Yigong Shi
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA
    Mol Cell 9:459-70. 2002
    ..This article reviews these latest advances and presents our current understanding of caspase regulation during apoptosis...
  8. ncbi Mechanisms of TGF-beta signaling from cell membrane to the nucleus
    Yigong Shi
    Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA
    Cell 113:685-700. 2003
    ..This article reviews these latest advances and presents our current understanding on the mechanisms of TGF-beta signaling from cell membrane to the nucleus...
  9. ncbi A structural view of mitochondria-mediated apoptosis
    Y Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nat Struct Biol 8:394-401. 2001
    ..Recent biochemical and structural studies reveal a molecular basis for these important events and identify an evolutionarily conserved mechanism of apoptosis from fruit flies to mammals...
  10. ncbi Structural insights on Smad function in TGFbeta signaling
    Y Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Bioessays 23:223-32. 2001
    ..Rather than giving a comprehensive review on Smad-mediated TGFbeta signaling, this review focuses on functional insights provided by recent structural studies and discusses several existing controversies...
  11. ncbi Caspase activation: revisiting the induced proximity model
    Yigong Shi
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Cell 117:855-8. 2004
    ..The evidence supporting these models is critically evaluated and other possible mechanisms for initiator caspase activation are discussed...
  12. pmc Caspase activation, inhibition, and reactivation: a mechanistic view
    Yigong Shi
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Protein Sci 13:1979-87. 2004
    ..Recent structural and biochemical studies have revealed the underlying molecular mechanisms for these processes in mammals and in Drosophila. This paper reviews these latest advances...
  13. ncbi Structure and activation mechanism of the Drosophila initiator caspase Dronc
    Nieng Yan
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, New Jersey 08544, USA
    J Biol Chem 281:8667-74. 2006
    ..This study revealed insights into mechanism of Dronc activation, and in conjunction with other observations, suggests diverse mechanisms for the activation of initiator caspases...
  14. ncbi Structure of the protein phosphatase 2A holoenzyme
    Yanhui Xu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 127:1239-51. 2006
    ..This structure reveals significant ramifications for understanding the function and regulation of PP2A...
  15. ncbi Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans
    Nieng Yan
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA
    Nature 437:831-7. 2005
    ..The released CED-4 dimer further dimerizes to form a tetramer, which facilitates the autoactivation of CED-3. Together, our studies provide important insights into the regulation of cell death activation in C. elegans...
  16. ncbi Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry
    Zhuoru Wu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nat Struct Mol Biol 13:1084-91. 2006
    ..Structural analysis suggests that substrate entry to the active site is probably gated by the movement of helix alpha5...
  17. ncbi Structure of a site-2 protease family intramembrane metalloprotease
    Liang Feng
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Science 318:1608-12. 2007
    ..The structure reveals how zinc embedded in an integral membrane protein can catalyze peptide cleavage...
  18. pmc Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway
    Min Hu
    Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
    PLoS Biol 4:e27. 2006
    ..These results, together with the structure of a combined substrate-binding-and-deubiquitylation domain of HAUSP, provide important insights into regulation of the p53-MDM2 pathway by HAUSP...
  19. ncbi Mechanism of XIAP-mediated inhibition of caspase-9
    Eric N Shiozaki
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 11:519-27. 2003
    ..Thus, XIAP sequesters caspase-9 in a monomeric state, which serves to prevent catalytic activity. These studies, in conjunction with other observations, define a unified mechanism for the activation of all caspases...
  20. doi Mechanism of substrate unfolding and translocation by the regulatory particle of the proteasome from Methanocaldococcus jannaschii
    Fan Zhang
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 34:485-96. 2009
    ..Sequence conservation suggests that the principles of PAN function are likely to apply to the proteasomal RP of eukaryotes...
  21. ncbi Structure of the apoptotic protease-activating factor 1 bound to ADP
    Stefan J Riedl
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA
    Nature 434:926-33. 2005
    ..Apaf-1 binds to and hydrolyses ATP/dATP and their analogues. The binding and hydrolysis of nucleotides seem to drive conformational changes that are essential for the formation of the apoptosome and the activation of caspase-9...
  22. ncbi Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins
    Yongna Xing
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, NJ 08544, USA
    Cell 127:341-53. 2006
    ..These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology...
  23. ncbi Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling
    Eric N Shiozaki
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 14:405-12. 2004
    ..Additional structural analysis revealed significant implications for understanding the function of the BRCT family of proteins in DNA damage and repair signaling...
  24. ncbi 2:1 Stoichiometry of the CED-4-CED-9 complex and the tetrameric CED-4: insights into the regulation of CED-3 activation
    Nieng Yan
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, New Jersey 08544, USA
    Cell Cycle 5:31-4. 2006
    ..On the basis of structural and biochemical analyses, working models are proposed to explain the mechanism by which CED-4 facilitates CED-3 activation...
  25. ncbi Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40
    Yu Chen
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nat Struct Mol Biol 14:527-34. 2007
    ..These findings suggest that ST may function mainly by inhibiting the phosphatase activity of the PP2A core enzyme, and to a lesser extent by modulating assembly of the PP2A holoenzymes...
  26. ncbi Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4
    Nieng Yan
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA
    Mol Cell 15:999-1006. 2004
    ..These data suggest a working mechanism for the release of CED-4 from the CED-4/CED-9 complex upon EGL-1 binding and provide a mechanistic framework for understanding apoptosis activation in C. elegans...
  27. pmc Engineering a dimeric caspase-9: a re-evaluation of the induced proximity model for caspase activation
    Yang Chao
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey, USA
    PLoS Biol 3:e183. 2005
    ..These findings suggest that dimerization of caspase-9 may be qualitatively different from its activation by Apaf-1, and in conjunction with other evidence, posit an induced conformation model for the activation of initiator caspases...
  28. ncbi Structure-activity based study of the Smac-binding pocket within the BIR3 domain of XIAP
    Aislyn D Wist
    Department of Chemistry, Princeton University, Princeton, NJ 08544, USA
    Bioorg Med Chem 15:2935-43. 2007
    ..The structures of BIR3-XIAP in complex with a Smac peptide and a peptide mimic were solved and analyzed to elucidate the structure-activity relationship surrounding the Smac-binding domain within BIR3-XIAP...
  29. ncbi Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective mechanism for haem
    Liang Feng
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nature 435:697-701. 2005
    ..The observed structural changes, which impair the chemical reactivity of haem iron, explain how AHSP stabilizes alphaHb and prevents its damaging effects in cells...
  30. pmc Structural insights into the regulatory particle of the proteasome from Methanocaldococcus jannaschii
    Fan Zhang
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 34:473-84. 2009
    ..These studies reveal structural codes and architecture of the complete proteasome, identify potential substrate-binding sites, and uncover unexpected asymmetry in the RP of archaea and eukaryotes...
  31. pmc Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation
    Yanhui Xu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 31:873-85. 2008
    ..The beta propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding beta hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau...
  32. pmc Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14
    Min Hu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ, USA
    EMBO J 24:3747-56. 2005
    ..These structural observations, in conjunction with biochemical characterization, identify important regulatory mechanisms for USP14...
  33. doi Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms
    Yan Xu
    Department of Ecology and Evolutionary Biology, Princeton University, New Jersey 08544, USA
    Nature 452:56-61. 2008
    ..Given the central role of diatoms in exporting carbon to the deep sea, their use of cadmium in an enzyme critical for carbon acquisition establishes a remarkable link between the global cycles of cadmium and carbon...
  34. ncbi Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding
    Jijie Chai
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, New Jersey 08544, USA
    J Biol Chem 278:20327-31. 2003
    ..Removal of the zinc atom results in compromised DNA binding activity. These results define the Smad MH1 domain as a zinc-coordinating module that exhibits unique DNA binding properties...
  35. ncbi Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim
    Nieng Yan
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA
    Nat Struct Mol Biol 11:420-8. 2004
    ..These studies define novel molecular mechanisms for the inhibition and activation of a representative D. melanogaster effector caspase...
  36. ncbi Structure and mechanism of the phosphotyrosyl phosphatase activator
    Yang Chao
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Mol Cell 23:535-46. 2006
    ..This function of PTPA strictly depends on the composite ATPase activity. These observations reveal significant insights into the function and mechanism of PTPA and have important ramifications for understanding PP2A function...
  37. ncbi Structure of Apaf-1 in the auto-inhibited form: a critical role for ADP
    Qing Bao
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, New Jersey 08544, USA
    Cell Cycle 4:1001-3. 2005
    ..elegans, it is unclear whether they employ similar mechanisms for their own activation and for activating caspases. Much of the underlying mechanisms remain to be investigated by structural biology and biochemistry...
  38. ncbi Structural basis of IAP recognition by Smac/DIABLO
    G Wu
    Department of Molecular Biology, Princeton University, New Jersey 08544, USA
    Nature 408:1008-12. 2000
    ..In addition to explaining a number of biological observations, our structural analysis identifies potential targets for drug screening...
  39. ncbi Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde
    Min Hu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 111:1041-54. 2002
    ..Binding by ubiquitin aldehyde induces a drastic conformational change in the active site that realigns the catalytic triad residues for catalysis...
  40. ncbi Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin
    Liang Feng
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 119:629-40. 2004
    ..These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb...
  41. ncbi Molecular mechanisms of caspase regulation during apoptosis
    Stefan J Riedl
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA
    Nat Rev Mol Cell Biol 5:897-907. 2004
    ..This article reviews these latest advances and describes our present understanding of caspase regulation during apoptosis...
  42. ncbi Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2
    Michael D Tibbetts
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Structure 12:2257-63. 2004
    ..Structural analyses provide insights into the possible function of this unique subfamily of FYVE-type domains...
  43. doi Structural mechanism of demethylation and inactivation of protein phosphatase 2A
    Yongna Xing
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, NJ 08544, USA
    Cell 133:154-63. 2008
    ..These observations identify a dual role of PME-1 that regulates PP2A activation, methylation, and holoenzyme assembly in cells...
  44. ncbi Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi
    Wenyu Li
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nat Struct Biol 9:436-41. 2002
    ..These structural and biochemical observations provide an important framework for deciphering the mechanisms of HtrA2/Omi-mediated apoptosis...
  45. doi Structure and mechanism of the S component of a bacterial ECF transporter
    Peng Zhang
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nature 468:717-20. 2010
    ....
  46. ncbi Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination
    Jijie Chai
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA
    Nat Struct Biol 10:892-8. 2003
    ..These observations reveal the molecular mechanisms of how DIAP1 recognizes Dronc, and more importantly, how the RHG proteins remove DIAP1-mediated ubiquitination of Dronc...
  47. ncbi Crystal structure of a viral FLIP: insights into FLIP-mediated inhibition of death receptor signaling
    Feng Yen Li
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, New Jersey 08544, USA
    J Biol Chem 281:2960-8. 2006
    ..These observations, in conjunction with published evidence, reveal significant insights into the function of v-FLIP and suggest a mechanism by which v-FLIP and c-FLIPS inhibit death receptor signaling...
  48. ncbi Structural mechanism of Smad4 recognition by the nuclear oncoprotein Ski: insights on Ski-mediated repression of TGF-beta signaling
    Jia Wei Wu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 111:357-67. 2002
    ..Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding...
  49. ncbi Structural basis of Smad2 recognition by the Smad anchor for receptor activation
    G Wu
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, NJ 08544, USA
    Science 287:92-7. 2000
    ..Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors...
  50. pmc Crystal structure of the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase region
    Jong W Yu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Proc Natl Acad Sci U S A 108:21004-9. 2011
    ..This structure serves as an important framework for deciphering the function and mechanism of paracaspases exemplified by MALT1...
  51. pmc Mechanism of procaspase-8 activation by c-FLIPL
    Jong W Yu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Proc Natl Acad Sci U S A 106:8169-74. 2009
    ..Together, these findings provide molecular insights into a key aspect of c-FLIP(L) function that modulates procaspase-8 activation to elicit diverse responses in different cellular contexts...
  52. ncbi Structural and biochemical basis of apoptotic activation by Smac/DIABLO
    J Chai
    Department of Molecular Biology, Princeton University, New Jersey 08544, USA
    Nature 406:855-62. 2000
    ..These results establish an evolutionarily conserved structural and biochemical basis for the activation of apoptosis by Smac/DIABLO...
  53. ncbi Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling
    J W Wu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 8:1277-89. 2001
    ..These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways...
  54. doi A structural basis for the reduced toxicity of dinophysistoxin-2
    Jason Huhn
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Washington Road, Princeton, New Jersey 08544, USA
    Chem Res Toxicol 22:1782-6. 2009
    ..These results highlight the potential of molecular modeling studies for understanding the relative toxicity of analogues once the binding site at the molecular target has been properly characterized...
  55. ncbi Structural basis of caspase-7 inhibition by XIAP
    J Chai
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA
    Cell 104:769-80. 2001
    ..Our biochemical and structural analyses reveal that the BIR domains are dispensable for the inhibition of caspase-3 and -7. This study provides a structural basis for the design of the next-generation caspase inhibitors...
  56. ncbi Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1
    Qing Bao
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 25:181-92. 2007
    ..Consequently, calcium blocks the ability of Apaf-1 to activate caspase-9. These observations suggest an important role of calcium homeostasis on the Apaf-1-dependent apoptotic pathway...
  57. ncbi Mechanisms of apoptosis through structural biology
    Nieng Yan
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Annu Rev Cell Dev Biol 21:35-56. 2005
    ..Although an emphasis is given to the mammalian pathways, a comparative analysis is applied to related mechanistic information in Drosophila and Caenorhabditis elegans...
  58. ncbi Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides
    J W Wu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 8:95-104. 2001
    ..Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins...
  59. ncbi Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1
    H Qin
    Department of Chemistry, Princeton University, New Jersey 08544, USA
    Nature 399:549-57. 1999
    ....
  60. ncbi Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling
    Y Shi
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, New Jersey 08544, USA
    Cell 94:585-94. 1998
    ..This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-beta-responsive genes...
  61. doi FLIP and the death effector domain family
    J W Yu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ, 08544 USA
    Oncogene 27:6216-27. 2008
    ....
  62. pmc Oligomerization and activation of caspase-9, induced by Apaf-1 CARD
    Eric N Shiozaki
    Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA
    Proc Natl Acad Sci U S A 99:4197-202. 2002
    ..Based on these observations, we discuss the implications of this complex on the observed Apaf-1 function...
  63. ncbi Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding
    J Chai
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 107:399-407. 2001
    ..These analyses reveal the structural mechanisms of caspase activation and demonstrate that the inhibitor/substrate binding is a process of induced fit...
  64. ncbi Molecular targeting of inhibitor of apoptosis proteins based on small molecule mimics of natural binding partners
    Rachael A Kipp
    Department of Chemistry, Frick Laboratory, Princeton University, Washington Road, Princeton, NJ 08544, USA
    Biochemistry 41:7344-9. 2002
    ..The results permit residue-specific analysis of the interaction. Furthermore, we show that hydrophobic effects in the fourth position are general and can effectively increase overall affinity...
  65. pmc The 1.9 A crystal structure of Escherichia coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis
    S Ha
    Department of Chemistry, Princeton University, New Jersey 08544, USA
    Protein Sci 9:1045-52. 2000
    ..The identification of a conserved structural motif involved in donor binding in different UDP-sugar transferases also suggests that it may be possible to identify--and perhaps alter--the residues that help determine donor specificity...
  66. ncbi Computational EST database analysis identifies a novel member of the neuropoietic cytokine family
    Y Shi
    Department of Molecular Biology, Department of Pharmacology, Department of Protein Expression, Human Genome Sciences, Inc, 9410 Key West Avenue, Rockville, Maryland 20850, USA
    Biochem Biophys Res Commun 262:132-8. 1999
    ..Furthermore, the signal transduction pathway for CLC was characterized in the neuroblastoma cell line SK-N-MC and found to involve tyrosine phosphorylation of gp130 and STAT-1...
  67. ncbi Apoptosome: a platform for the activation of initiator caspases
    Q Bao
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell Death Differ 14:56-65. 2007
    ....
  68. ncbi Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant
    J Y Sze
    Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Nature 403:560-4. 2000
    ..The action of the C. elegans serotonergic system in metabolic control is similar to mammalian serotonergic input to metabolism and obesity...
  69. pmc Inhibition of CED-3 zymogen activation and apoptosis in Caenorhabditis elegans by caspase homolog CSP-3
    Xin Geng
    Department of Molecular, Cellular, and Developmental Biology, Campus Box 347, University of Colorado, Boulder, Colorado 80309, USA
    Nat Struct Mol Biol 15:1094-101. 2008
    ..However, CSP-3 does not block CED-3 activation induced by CED-4, nor does it inhibit the activity of the activated CED-3 protease. Therefore CSP-3 uses a previously unreported mechanism to protect cells from apoptosis...
  70. pmc Multiple apoptotic caspase cascades are required in nonapoptotic roles for Drosophila spermatid individualization
    Jun R Huh
    Division of Biology, California Institute of Technology, Pasadena, California, USA
    PLoS Biol 2:E15. 2004
    ..Our results demonstrate that multiple caspases and caspase regulators, likely acting at distinct points in time and space, are required for spermatid individualization, a nonapoptotic process...
  71. ncbi Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans
    Xiaochen Wang
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Science 298:1587-92. 2002
    ..Thus, AIF and EndoG define a single, mitochondria-initiated apoptotic DNA degradation pathway that is conserved between C. elegans and mammals...
  72. ncbi A conserved tetrapeptide motif: potentiating apoptosis through IAP-binding
    Yigong Shi
    Cell Death Differ 9:93-5. 2002
  73. pmc sickle, a novel Drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein
    Srinivasa M Srinivasula
    The Center for Apoptosis Research, Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Curr Biol 12:125-30. 2002
    ..These findings point to conservation in the structure and function of the IAP-inhibitory proteins across species and suggest the existence of other family members...
  74. ncbi PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling
    Xia Lin
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 125:915-28. 2006
    ..This work demonstrates that PPM1A/PP2Calpha, through dephosphorylation of Smad2/3, plays a critical role in terminating TGFbeta signaling...
  75. ncbi C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1
    Xiaochen Wang
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Nat Cell Biol 9:541-9. 2007
    ..Thus WAH-1, after its release from mitochondria during apoptosis, promotes plasma membrane phosphatidylserine externalization through its downstream effector, SCRM-1...
  76. pmc Transforming growth factor beta-mediated transcriptional repression of c-myc is dependent on direct binding of Smad3 to a novel repressive Smad binding element
    Joshua P Frederick
    Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA
    Mol Cell Biol 24:2546-59. 2004
    ....
  77. ncbi RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in Caenorhabditis elegans
    Chonglin Yang
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA
    J Biol Chem 281:9137-44. 2006
    ..These findings suggest that RNA aptamers can be used to modulate programmed cell death in vivo and can potentially be used to develop drugs to treat human diseases caused by abnormal apoptosis...
  78. pmc Direct binding of DNA by tumor suppressor menin
    Ping La
    Abramson Family Cancer Research Institute, Department of Cancer Biology and Signal Transduction Program, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6160, USA
    J Biol Chem 279:49045-54. 2004
    ..Collectively, these results demonstrate, for the first time, a novel biochemical activity of menin, binding to DNA, and link its DNA binding to the regulation of cell proliferation...
  79. ncbi A high-throughput screen for identification of molecular mimics of Smac/DIABLO utilizing a fluorescence polarization assay
    Constance J Glover
    Developmental Therapeutics Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA
    Anal Biochem 320:157-69. 2003
    ..This robust assay offers potential for high-throughput screening discovery of novel compounds simulating the action of Smac/DIABLO...
  80. pmc Structural basis for antiactivation in bacterial quorum sensing
    Guozhou Chen
    Department of Biology, Indiana University, 915 East Third Street, Bloomington, IN 47405, USA
    Proc Natl Acad Sci U S A 104:16474-9. 2007
    ..In addition, the structural basis of antiactivation presents a regulatory interaction that provides general insights relevant to the field of transcription regulation and signal transduction...
  81. ncbi Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia
    Mitchell J Weiss
    The Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA
    Ann N Y Acad Sci 1054:103-17. 2005
    ..Moreover, understanding how AHSP stabilizes alphaHb provides a theoretical basis for new strategies to inhibit the damaging effects of free alphaHb that accumulates in beta-thalassemia...
  82. ncbi A structure of the human apoptosome at 12.8 A resolution provides insights into this cell death platform
    Xinchao Yu
    Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Structure 13:1725-35. 2005
    ..This model provides insights into the roles of dATP and cytochrome c in assembly. Our structure also reveals how a CARD ring and the central hub combine to create a platform for procaspase-9 activation...
  83. pmc Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate
    Rosanna P Baker
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 507 Preclinical Teaching Building, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 104:8257-62. 2007
    ..Moreover, our mutagenesis also underscores the importance of other residue interactions within the enzyme that warrant further scrutiny...
  84. ncbi Allosteric activation of a bacterial stress sensor
    Nieng Yan
    Center for Structural Biology, Institute of Biomedicine, Tsinghua University, Beijing, China
    Cell 131:441-3. 2007
    ..Now Sohn et al. (2007) show conclusively that inhibition of DegS is relieved allosterically by binding of the C-terminal sequences in unfolded OMPs to the PDZ domain of DegS...
  85. ncbi Histone H1.2 as a trigger for apoptosis
    Nieng Yan
    Nat Struct Biol 10:983-5. 2003

Research Grants41

  1. SMAD Proteins in TGF-Beta Signaling - structural studies
    Yigong Shi; Fiscal Year: 2007
    ..In particular, we will be able to examine the effects of the tumorigenic mutations on the assembly of an active transcriptional complex. ..
  2. Structural biololgy of tumor suppressor PP2A and its regulatory proteins
    Yigong Shi; Fiscal Year: 2010
    ..The generally excellent solution properties of the proteins and their cognate complexes make this undertaking feasible. ..
  3. Structural Biology of Intramembrane Proteolysis
    Yigong Shi; Fiscal Year: 2010
    ..This proposal seeks to understand the structures and mechanisms of these intramembrane proteases. ..
  4. Structural biololgy of tumor suppressor PP2A and its regulatory proteins
    Yigong Shi; Fiscal Year: 2007
    ..The generally excellent solution properties of the proteins and their cognate complexes make this undertaking feasible. ..
  5. Structural Studies of Caspase Activation in Apoptosis
    Yigong Shi; Fiscal Year: 2007
    ..This specific aim, together with the closely related structural studies, will reveal comprehensive mechanisms that govern the activation of caspase-8 by DISC and the suppression of this process by FLIPs. ..
  6. HAUSP-mediated Deubiquitination of p53
    Yigong Shi; Fiscal Year: 2007
    ..4) Determination of the structures of the full-length HAUSP by itself and bound to p53. This study will reveal the regulation of HAUSP-mediated p53 deubiquitination. ..
  7. Structural/Biochemical Analysis: Apoptosis in C. elegans
    Yigong Shi; Fiscal Year: 2007
    ..CED3 forms a holoenzyme with oligomeric CED4. A CED4-CED3 complex has been reconstituted in vitro. The complex will be crystallized and its three-dimensional structure will be determined. ..
  8. Structural Studies of Caspase Activation in Apoptosis
    Yigong Shi; Fiscal Year: 2006
    ..This specific aim, together with the closely related structural studies, will reveal comprehensive mechanisms that govern the activation of caspase-8 by DISC and the suppression of this process by FLIPs. ..
  9. SMAD Proteins in TGF-Beta Signaling - structural studies
    Yigong Shi; Fiscal Year: 2006
    ..In particular, we will be able to examine the effects of the tumorigenic mutations on the assembly of an active transcriptional complex. ..
  10. HAUSP-mediated Deubiquitination of p53
    Yigong Shi; Fiscal Year: 2006
    ..4) Determination of the structures of the full-length HAUSP by itself and bound to p53. This study will reveal the regulation of HAUSP-mediated p53 deubiquitination. ..
  11. Structural Studies of Caspase Activation in Apoptosis
    Yigong Shi; Fiscal Year: 2010
    ..This specific aim, together with the closely related structural studies, will reveal comprehensive mechanisms that govern the activation of caspase-8 by DISC and the suppression of this process by FLIPs. ..
  12. Structural Biology of Intramembrane Proteolysis
    Yigong Shi; Fiscal Year: 2009
    ..This proposal seeks to understand the structures and mechanisms of these intramembrane proteases. ..
  13. Structural Studies of Caspase Activation in Apoptosis
    Yigong Shi; Fiscal Year: 2009
    ..This specific aim, together with the closely related structural studies, will reveal comprehensive mechanisms that govern the activation of caspase-8 by DISC and the suppression of this process by FLIPs. ..
  14. Structural biololgy of tumor suppressor PP2A and its regulatory proteins
    Yigong Shi; Fiscal Year: 2009
    ..The generally excellent solution properties of the proteins and their cognate complexes make this undertaking feasible. ..
  15. Structural Studies of Apoptosome Assembly in Apoptosis
    Yigong Shi; Fiscal Year: 2006
    ..This 1.4 MDa complex will be crystallized. The structure will be determined by either molecular replacement or by multiple isomorphous replacement. ..
  16. Structural/Biochemical Analysis: Apoptosis in C. elegans
    Yigong Shi; Fiscal Year: 2006
    ..CED3 forms a holoenzyme with oligomeric CED4. A CED4-CED3 complex has been reconstituted in vitro. The complex will be crystallized and its three-dimensional structure will be determined. ..
  17. HAUSP-mediated Deubiquitination of p53
    Yigong Shi; Fiscal Year: 2005
    ..4) Determination of the structures of the full-length HAUSP by itself and bound to p53. This study will reveal the regulation of HAUSP-mediated p53 deubiquitination. ..
  18. Structural Studies of Apoptosome Assembly in Apoptosis
    Yigong Shi; Fiscal Year: 2003
    ..This 1.4 MDa complex will be crystallized. The structure will be determined by either molecular replacement or by multiple isomorphous replacement. ..
  19. HAUSP-mediated Deubiquitination of p53
    Yigong Shi; Fiscal Year: 2003
    ..4) Determination of the structures of the full-length HAUSP by itself and bound to p53. This study will reveal the regulation of HAUSP-mediated p53 deubiquitination. ..
  20. Structural Studies in Apaf 1 mediated Apoptosis
    Yigong Shi; Fiscal Year: 2002
    ..The crystals of procaspase-9 by itself and in complex with an inhibitory c-IAP1 fragment will be generated; these structures will be determined by either molecular replacement or multiple isomorphous replacement. ..
  21. Structural Studies of Apoptosome Assembly in Apoptosis
    Yigong Shi; Fiscal Year: 2002
    ..This 1.4 MDa complex will be crystallized. The structure will be determined by either molecular replacement or by multiple isomorphous replacement. ..
  22. Structural Studies in Apaf 1 mediated Apoptosis
    Yigong Shi; Fiscal Year: 2001
    ..The crystals of procaspase-9 by itself and in complex with an inhibitory c-IAP1 fragment will be generated; these structures will be determined by either molecular replacement or multiple isomorphous replacement. ..
  23. Structural Studies in Apaf 1 mediated Apoptosis
    Yigong Shi; Fiscal Year: 2003
    ..The crystals of procaspase-9 by itself and in complex with an inhibitory c-IAP1 fragment will be generated; these structures will be determined by either molecular replacement or multiple isomorphous replacement. ..
  24. Structural Studies of Apoptosome Assembly in Apoptosis
    Yigong Shi; Fiscal Year: 2005
    ..This 1.4 MDa complex will be crystallized. The structure will be determined by either molecular replacement or by multiple isomorphous replacement. ..
  25. SMAD Proteins in TGF-Beta Signaling - structural studies
    Yigong Shi; Fiscal Year: 2005
    ..In particular, we will be able to examine the effects of the tumorigenic mutations on the assembly of an active transcriptional complex. ..
  26. Structural Studies in Apaf 1 mediated Apoptosis
    Yigong Shi; Fiscal Year: 2005
    ..The crystals of procaspase-9 by itself and in complex with an inhibitory c-IAP1 fragment will be generated; these structures will be determined by either molecular replacement or multiple isomorphous replacement. ..
  27. SMAD Proteins in TGF-Beta Signaling - structural studies
    Yigong Shi; Fiscal Year: 2004
    ..In particular, we will be able to examine the effects of the tumorigenic mutations on the assembly of an active transcriptional complex. ..
  28. Apoptosis in Biochemistry and Structural Biology
    Yigong Shi; Fiscal Year: 2004
    ..By all criteria, this symposium promises to be a unique and one of the most exciting meetings in apoptosis in recent years. ..
  29. HAUSP-mediated Deubiquitination of p53
    Yigong Shi; Fiscal Year: 2004
    ..4) Determination of the structures of the full-length HAUSP by itself and bound to p53. This study will reveal the regulation of HAUSP-mediated p53 deubiquitination. ..
  30. Structural Studies of Apoptosome Assembly in Apoptosis
    Yigong Shi; Fiscal Year: 2004
    ..This 1.4 MDa complex will be crystallized. The structure will be determined by either molecular replacement or by multiple isomorphous replacement. ..
  31. Structural Studies in Apaf 1 mediated Apoptosis
    Yigong Shi; Fiscal Year: 2004
    ..The crystals of procaspase-9 by itself and in complex with an inhibitory c-IAP1 fragment will be generated; these structures will be determined by either molecular replacement or multiple isomorphous replacement. ..
  32. STRUCTURAL STUDIES OF SMAD PROTEINS IN TGF BETA SIGNALIN
    Yigong Shi; Fiscal Year: 1999