Research Topics
Genomes and Genes | Yue Ming LiSummaryAffiliation: Memorial Sloan-Kettering Cancer Center Country: USA Publications
Research Grants
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Detail Information
Publications
Soluble oligomers of the intramembrane serine protease YqgP are catalytically active in the absence of detergentsXiaojun Lei
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Biochemistry 47:11920-9. 2008..Therefore, this work not only provides a unique system for elucidating the reaction mechanism of rhomboid but also will facilitate the characterization of other intramembrane proteases as well as non-protease membrane proteins...
An exo-cell assay for examining real-time gamma-secretase activity and inhibitionChristopher C Shelton
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Mol Neurodegener 4:22. 2009....
Structure of gamma-secretase and its trimeric pre-activation intermediate by single-particle electron microscopyFabiana Renzi
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
J Biol Chem 286:21440-9. 2011..Comparison with the structure of a trimeric pre-activation intermediate suggested that the incorporation of PEN-2 might contribute to the maturation of the active site architecture...
BMS-708,163 targets presenilin and lacks notch-sparing activityChristina J Crump
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States
Biochemistry 51:7209-11. 2012..Furthermore, BMS-708,163 blocks the binding of four different active site-directed GSI photoaffinity probes. We therefore report that this compound acts as a nonselective γ-secretase inhibitor...
Activation and intrinsic gamma-secretase activity of presenilin 1Kwangwook Ahn
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065
Proc Natl Acad Sci U S A 107:21435-40. 2010..Thus, we conclusively establish that activated PS is catalytically competent and the bimolecular interaction of PS1 and PEN2 can convert the PS1 zymogen to an active protease...
Modulation of gamma-secretase specificity using small molecule allosteric inhibitorsChristopher C Shelton
Molecular Pharmacology and Chemistry Program and High Throughput Screening Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Proc Natl Acad Sci U S A 106:20228-33. 2009..Furthermore, this class of selective inhibitors provides the basis for development of Alzheimer disease therapeutic agents...
An APP inhibitory domain containing the Flemish mutation residue modulates gamma-secretase activity for Abeta productionYuan Tian
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Nat Struct Mol Biol 17:151-8. 2010....
Dual role of alpha-secretase cleavage in the regulation of gamma-secretase activity for amyloid productionYuan Tian
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
J Biol Chem 285:32549-56. 2010..This work reveals an unforeseen role for α-secretase in generating an endogenous γ-secretase inhibitor that down-regulates the production of Aβ. Deregulation of this feedback mechanism may contribute to the pathogenesis of AD...
Processing of Notch and amyloid precursor protein by gamma-secretase is spatially distinctLeonid Tarassishin
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Proc Natl Acad Sci U S A 101:17050-5. 2004..Furthermore, the fact that inhibitors first target gamma-secretase in the plasma membrane for Notch processing, and not for APP, will have important implications for drug development to treat Alzheimer's disease and cancer...
Familial Alzheimer disease presenilin-1 mutations alter the active site conformation of γ-secretaseDe Ming Chau
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
J Biol Chem 287:17288-96. 2012....
Stereo-controlled synthesis of novel photoreactive gamma-secretase inhibitorsGuangli Yang
Organic Synthesis Core Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Bioorg Med Chem Lett 19:922-5. 2009..Compounds 2 and 3 are potent gamma-secretase inhibitors and directly interact with presenilin-1, a catalytic subunit of gamma-secretase...
Development of clickable active site-directed photoaffinity probes for γ-secretaseChristina J Crump
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Bioorg Med Chem Lett 22:2997-3000. 2012....
A miniaturized 1536-well format gamma-secretase assayChristopher C Shelton
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Assay Drug Dev Technol 7:461-70. 2009..This validated assay can readily be used for primary screening against large chemical libraries searching for novel inhibitors of gamma-secretase activity that may represent potential therapeutics for AD and a variety of neoplasms...
Characterization of an atypical gamma-secretase complex from hematopoietic originLisa Placanica
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Biochemistry 49:2796-804. 2010..These data underscore the need for studying endogenous gamma-secretase to fully understand of the biology of gamma-secretase and its complexity as a molecular target for the development of disease therapeutics...
High-throughput identification of inhibitors of human mitochondrial peptide deformylaseChristophe Antczak
High Throughput Screening Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Biomol Screen 12:521-35. 2007....
{gamma}-Secretase Substrate Concentration Modulates the Abeta42/Abeta40 Ratio: IMPLICATIONS FOR ALZHEIMER DISEASEYe Ingrid Yin
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021 and Department of Biology, Rensselaer Polytechnic Institute, Troy, New York 12180
J Biol Chem 282:23639-44. 2007..Therefore, strategies lowering the Abeta42/Abeta40 ratio through partial reduction of gamma-secretase substrate production may introduce a practical therapeutic modality for treatment of AD...
A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/DiabloZhonghua Gao
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
J Biol Chem 282:30718-27. 2007..We also show that XIAP homotrimerizes via its C-terminal Ring domain, making its inhibitory activity toward caspase-3 more susceptible to Smac...
Pen2 and presenilin-1 modulate the dynamic equilibrium of presenilin-1 and presenilin-2 gamma-secretase complexesLisa Placanica
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
J Biol Chem 284:2967-77. 2009....
The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activityXiaojun Lei
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
J Mol Biol 394:815-25. 2009....
gamma-Secretase inhibitors abrogate oxaliplatin-induced activation of the Notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivityRaymond D Meng
Department of Medicine, Division of Solid Tumor Oncology, Laboratory of New Drug Development, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Cancer Res 69:573-82. 2009..Therefore, combining GSIs with chemotherapy may represent a novel approach for treating metastatic colon cancers by mitigating the development of chemoresistance...
Gender- and age-dependent gamma-secretase activity in mouse brain and its implication in sporadic Alzheimer diseaseLisa Placanica
Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
PLoS ONE 4:e5088. 2009..In addition, deceased Notch gamma-secretase activity may also contribute to neurodegeneration. Therefore, this study implicates altered gamma-secretase activity and specificity as a possible mechanism of sporadic AD during aging...
Research Grants
- Regulation and function of gamma-secretaseYueming Li; Fiscal Year: 2007..Moreover, these investigations will facilitate the development of potent and specific inhibitors of gamma-secretase for potential AD therapies. ..
- Regulation and function of gamma-secretaseYueming Li; Fiscal Year: 2009..Moreover, these investigations will facilitate the development of potent and specific inhibitors of gamma-secretase for potential AD therapies. ..
