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Rac1 changes the substrate specificity of gamma-secretase between amyloid precursor protein and Notch1
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Boo, Jung Hyun | - |
dc.contributor.author | Sohn, Ji Hoon | - |
dc.contributor.author | Kim, Ji Eun | - |
dc.contributor.author | Song, Hyundong | - |
dc.contributor.author | Mook-Jung, Inhee | - |
dc.date.accessioned | 2010-06-06T23:27:42Z | - |
dc.date.available | 2010-06-06T23:27:42Z | - |
dc.date.issued | 2008-06-10 | - |
dc.identifier.citation | Biochemical and Biophysical Research Communications 372(4):913-917 | en |
dc.identifier.issn | 1090-2104 (Electronic) | - |
dc.identifier.uri | http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WBK-4SNY56P-1-9&_cdi=6713&_user=168665&_orig=search&_coverDate=08%2F08%2F2008&_sk=996279995&view=c&wchp=dGLbVlb-zSkzk&md5=88b81f70dc1aa61118fd67c88c4e960e&ie=/sdarticle.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/67439 | - |
dc.description.abstract | Beta amyloid peptide is generated from amyloid precursor protein (APP) by proteolytic cleavage of beta- and gamma-secretases, and plays a critical role in the pathogenesis of Alzheimer's disease. Since gamma-secretase cleaves several proteins including APP and Notch in a number of cell types, it is important to understand the conditions determining gamma-secretase substrate specificity. In the present study, inhibition of Rac1 attenuated gamma-secretase activity for APP, resulting in decreased production of the APP intracellular domain but accumulated C-terminal fragments (APP-CTF). In contrast, Rac1 inhibitor, NSC23766 increased production of the Notch1 intracellular domain but slightly decreased the ectodomain-shed form of Notch1 (NotchDeltaE). To elucidate the mechanism underlying these observations, we performed co-immunoprecipitation experiments to analyze the interaction between Rac1 and presenilin1 (PS1), a component of the gamma-secretase complex. Inhibition of Rac1 enhanced its interaction with PS1. Under the same condition, PS1 interacted more strongly with NotchDeltaE than with APP-CTF. Our results suggested that PS1 determines the preferred substrate for gamma-secretase between APP and Notch1, depending on the activation status of Rac1. | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | Alzheimer Disease/drug therapy/metabolism | en |
dc.subject | Aminoquinolines/pharmacology | en |
dc.subject | Amyloid Precursor Protein Secretases/*metabolism | en |
dc.subject | Amyloid beta-Protein/metabolism | en |
dc.subject | Amyloid beta-Protein Precursor/*metabolism | en |
dc.subject | Animals | en |
dc.subject | COS Cells | en |
dc.subject | Cell Line | en |
dc.subject | Cercopithecus aethiops | en |
dc.subject | Drug Design | en |
dc.subject | Enzyme Activation | en |
dc.subject | Humans | en |
dc.subject | Presenilin-1/metabolism | en |
dc.subject | Protein Structure, Tertiary | en |
dc.subject | Pyrimidines/pharmacology | en |
dc.subject | Receptor, Notch1/genetics/*metabolism | en |
dc.subject | Sequence Deletion | en |
dc.subject | Substrate Specificity | en |
dc.subject | rac1 GTP-Binding Protein/antagonists & inhibitors/genetics/*metabolism | en |
dc.title | Rac1 changes the substrate specificity of gamma-secretase between amyloid precursor protein and Notch1 | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 부정현 | - |
dc.contributor.AlternativeAuthor | 손지훈 | - |
dc.contributor.AlternativeAuthor | 김지은 | - |
dc.contributor.AlternativeAuthor | 송현동 | - |
dc.identifier.doi | 10.1016/j.bbrc.2008.05.153 | - |
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